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General Information:

Id:	14,021
Diseases:	Alzheimer disease - [OMIM] Metabolic
Organism:	Rattus norvegicus
Gender:	female
Organism Model:	90 young or middle-aged female Sprague-Dawley rats, a rat model recapitulating fundamental characteristics of the human perimenopause
Publication type:	article/cited
Reference:	Yin F et al.(2015) The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity Neurobiol Aging 36: 2282-2295 [PMID: 25921624]

Interaction Information:

Comment	The perimenopause is an aging transition unique to the female that leads to reproductive senescence which can be characterized by multiple neurological symptoms. (cited information)
Formal Description Interaction-ID: 132448	process menopause transition increases_activity of process reproductive senescence

Comment	Gene expression analyses indicated two distinct aging programs: chronological and endocrine.
Formal Description Interaction-ID: 132467	process chronological aging affects_activity of process gene expression

Comment	Gene expression analyses indicated two distinct aging programs: chronological and endocrine.
Formal Description Interaction-ID: 132468	process endocrine aging affects_activity of process gene expression

Comment	The endocrine transition state manifested by irregular cycling thus emerged as a critical period for bioenergetic function.
Formal Description Interaction-ID: 132469	process endocrine transition to perimenopause increases_activity of phenotype irregular cycling

Comment	Similar to the human, rodent and nonhuman primates share common features of the perimenopausal transition, including decline in follicles, irregular cycling, irregular fertility, steroid hormone fluctuations and insensitivity to estrogen. (cited information)
Formal Description Interaction-ID: 132505	process menopause transition increases_activity of phenotype decreased ovarian follicle number

Comment	In humans and rodents, ovarian senescence from follicular depletion is associated with decreasing fecundity and increasing irregularity of estrus cycles.
Formal Description Interaction-ID: 132506	process ovarian senescence increases_activity of phenotype reduced fertility in humans and rodents; ovarian senescence from follicular depletion

Comment	The expression of glucose transporter 3 (GLUT3), pyruvate dehydrogenase E1alpha subunit (PDH-E1alpha), and ATPAF2 were decreased in the hippocampus of 9-10 m irregular cyclers.
Formal Description Interaction-ID: 132507	process menopause transition decreases_expression of gene/protein SLC2A3 in the hippocampus of 9-10 m irregular cyclers; compared to 9‚Äď10 month regular cyclers

Comment	It was also shown that the decline in brain glucose uptake is associated with a decrease in neuronal glucose transporter GLUT3 as reported in a previous study on female brain aging. (cited information)
Formal Description Interaction-ID: 132508	phenotype decreased SLC2A3 expression increases_activity of phenotype decreased cellular glucose uptake in female brain

Comment	The estrogen-controlled glucose metabolism appears to be replaced by ketone body metabolism when the rats transitioned from irregular cycling to acyclic, as suggested by increased expression of fatty acid metabolism-related gene (Cpt2) and mitochondria-related genes (Atpaf2 and Esrra) but unaltered glycolytic genes. This could represent an adaptive response of the midlife brain to enhance fatty acid metabolism and to utilize ketone bodies as alternative substrates due to declined glucose metabolism; the adaptive response was transient and lost with further chronological aging to 16 months.
Formal Description Interaction-ID: 132509	drug/chemical compound Estrogen affects_activity of process glucose metabolic process

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant decline in the expression of genes involved in molecule transport (heat shock 60 kDa protein 1 (HSPD1) and Bcl2/adenovirus E1B interacting protein 1 (Bnip1)); mitochondrial redox enzymes glutaredoxin 2 (Glrx2) and peroxiredoxin 3 (Prx3); the glutamate decarboxylases (Gad1 and Gad2, which generate the neurotransmitter GABA), and a neuronal survival gene (chemokine receptor Cxrcr4).
Formal Description Interaction-ID: 132510	process menopause transition decreases_expression of gene/protein HSPD1 in 9‚Äď10 month regular cyclers; compared to 6-month cyclers

Comment	Similar to the human, rodent and nonhuman primates share common features of the perimenopausal transition, including decline in follicles, irregular cycling, irregular fertility, steroid hormone fluctuations and insensitivity to estrogen. (cited information)
Formal Description Interaction-ID: 132511	process menopause transition increases_activity of phenotype irregular cycling

Comment	Similar to the human, rodent and nonhuman primates share common features of the perimenopausal transition, including decline in follicles, irregular cycling, irregular fertility, steroid hormone fluctuations and insensitivity to estrogen. (cited information)
Formal Description Interaction-ID: 132512	process menopause transition increases_activity of phenotype abnormal fertility/fecundity

Comment	Similar to the human, rodent and nonhuman primates share common features of the perimenopausal transition, including decline in follicles, irregular cycling, irregular fertility, steroid hormone fluctuations and insensitivity to estrogen. (cited information)
Formal Description Interaction-ID: 132513	process menopause transition increases_activity of phenotype irregular steroid hormone fluctuation

Comment	Similar to the human, rodent and nonhuman primates share common features of the perimenopausal transition, including decline in follicles, irregular cycling, irregular fertility, steroid hormone fluctuations and insensitivity to estrogen. (cited information)
Formal Description Interaction-ID: 132514	process menopause transition increases_activity of phenotype insensitivity to estrogen

Comment	In humans and rodents, ovarian senescence from follicular depletion is associated with decreasing fecundity and increasing irregularity of estrus cycles.
Formal Description Interaction-ID: 132515	process ovarian senescence increases_activity of phenotype abnormal estrous cycle in humans and rodents

Comment	The transition to irregular cycles was associated with cognitive impairments and altered sex steroids in hippocampus and cerebral cortex, while altered expression of estrogen receptor alpha (ERalpha) were found in astrocytes of cerebral cortex with altered neurotrophic activity in vitro.
Formal Description Interaction-ID: 132516	process transition to irregular cycles cooccurs with phenotype cognitive impairment

Comment	An increase in body weight was observed between the 6 month- and the 9‚Äď10 month-old regular cyclers and was constant for all subsequent stages.
Formal Description Interaction-ID: 132517	process aging increases_activity of phenotype increased body weight between the 6 month- and the 9‚Äď10 month-old regular cyclers

Comment	The expression of glucose transporter 3 (GLUT3), pyruvate dehydrogenase E1alpha subunit (PDH-E1alpha), and ATPAF2 were decreased in the hippocampus of 9-10 m irregular cyclers.
Formal Description Interaction-ID: 132518	process menopause transition decreases_expression of gene/protein PDHA1 in the hippocampus of 9-10 m irregular cyclers; compared to 9-10 m regular cyclers
Drugbank entries	Show/Hide entries for PDHA1
Drugbank DB00157	NADH not specified PDHA1
Drugbank DB00157	NADH not specified PDHA1

Comment	The expression of glucose transporter 3 (GLUT3), pyruvate dehydrogenase E1alpha subunit (PDH-E1alpha), and ATPAF2 were decreased in the hippocampus of 9-10 m irregular cyclers.
Formal Description Interaction-ID: 132519	process menopause transition decreases_expression of gene/protein ATPAF2 in the hippocampus of 9-10 m irregular cyclers; compared to 9-10 m regular cyclers

Comment	The estrogen-controlled glucose metabolism appears to be replaced by ketone body metabolism when the rats transitioned from irregular cycling to acyclic, as suggested by increased expression of fatty acid metabolism-related gene (Cpt2) and mitochondria-related genes (Atpaf2 and Esrra) but unaltered glycolytic genes. This could represent an adaptive response of the midlife brain to enhance fatty acid metabolism and to utilize ketone bodies as alternative substrates due to declined glucose metabolism; the adaptive response was transient and lost with further chronological aging to 16 months.
Formal Description Interaction-ID: 132523	gene/protein CPT2 affects_activity of process fatty acid metabolic process
Drugbank entries	Show/Hide entries for CPT2
Drugbank DB00583	L-Carnitine not specified CPT2
Drugbank DB01074	Perhexiline inhibitor CPT2
Drugbank DB00583	L-Carnitine not specified CPT2

Comment	The estrogen-controlled glucose metabolism appears to be replaced by ketone body metabolism when the rats transitioned from irregular cycling to acyclic, as suggested by increased expression of fatty acid metabolism-related gene (Cpt2) and mitochondria-related genes (Atpaf2 and Esrra) but unaltered glycolytic genes. This could represent an adaptive response of the midlife brain to enhance fatty acid metabolism and to utilize ketone bodies as alternative substrates due to declined glucose metabolism; the adaptive response was transient and lost with further chronological aging to 16 months.
Formal Description Interaction-ID: 132524	process menopause transition increases_expression of gene/protein CPT2 when the rats transitioned from irregular cycling to acyclic
Drugbank entries	Show/Hide entries for CPT2
Drugbank DB00583	L-Carnitine not specified CPT2
Drugbank DB01074	Perhexiline inhibitor CPT2
Drugbank DB00583	L-Carnitine not specified CPT2

Comment	The estrogen-controlled glucose metabolism appears to be replaced by ketone body metabolism when the rats transitioned from irregular cycling to acyclic, as suggested by increased expression of fatty acid metabolism-related gene (Cpt2) and mitochondria-related genes (Atpaf2 and Esrra) but unaltered glycolytic genes. This could represent an adaptive response of the midlife brain to enhance fatty acid metabolism and to utilize ketone bodies as alternative substrates due to declined glucose metabolism; the adaptive response was transient and lost with further chronological aging to 16 months.
Formal Description Interaction-ID: 132525	process menopause transition increases_expression of gene/protein ESRRA when the rats transitioned from irregular cycling to acyclic
Drugbank entries	Show/Hide entries for ESRRA
Drugbank DB00197	Troglitazone inverse agonist ESRRA
Drugbank DB06833	1-CYCLOHEXYL-N-{[1-(4-METHYLPHENYL)-1H-I ... not specified ESRRA

Comment	The estrogen-controlled glucose metabolism appears to be replaced by ketone body metabolism when the rats transitioned from irregular cycling to acyclic, as suggested by increased expression of fatty acid metabolism-related gene (Cpt2) and mitochondria-related genes (Atpaf2 and Esrra) but unaltered glycolytic genes. This could represent an adaptive response of the midlife brain to enhance fatty acid metabolism and to utilize ketone bodies as alternative substrates due to declined glucose metabolism; the adaptive response was transient and lost with further chronological aging to 16 months.
Formal Description Interaction-ID: 132526	process menopause transition NOT affects_expression of gene/protein genes involved in glycolysis when the rats transitioned from irregular cycling to acyclic, transient response, lost with further chronological aging to 16 months

Comment	The transition to irregular cycles was associated with cognitive impairments and altered sex steroids in hippocampus and cerebral cortex, while altered expression of estrogen receptor alpha (ERalpha) were found in astrocytes of cerebral cortex with altered neurotrophic activity in vitro.
Formal Description Interaction-ID: 132527	process transition to irregular cycles cooccurs with phenotype cognitive impairment

Comment	The transition to irregular cycles was associated with cognitive impairments and altered sex steroids in hippocampus and cerebral cortex, while altered expression of estrogen receptor alpha (ERalpha) were found in astrocytes of cerebral cortex with altered neurotrophic activity in vitro.
Formal Description Interaction-ID: 132528	process transition to irregular cycles cooccurs with phenotype altered sex steroids in hippocampus and cerebral cortex

Comment	The transition to irregular cycles was associated with cognitive impairments and altered sex steroids in hippocampus and cerebral cortex, while altered expression of estrogen receptor alpha (ERalpha) were found in astrocytes of cerebral cortex with altered neurotrophic activity in vitro.
Formal Description Interaction-ID: 132529	process transition to irregular cycles cooccurs with phenotype altered ESR1 expression in astrocytes of cerebral cortex; with altered neurotrophic activity in vitro

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant decline in the expression of genes involved in molecule transport (heat shock 60 kDa protein 1 (HSPD1) and Bcl2/adenovirus E1B interacting protein 1 (Bnip1)); mitochondrial redox enzymes glutaredoxin 2 (Glrx2) and peroxiredoxin 3 (Prx3); the glutamate decarboxylases (Gad1 and Gad2, which generate the neurotransmitter GABA), and a neuronal survival gene (chemokine receptor Cxrcr4).
Formal Description Interaction-ID: 132530	process menopause transition decreases_expression of gene/protein BNIP1 in 9‚Äď10 month regular cyclers; compared to 6-month cyclers

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant increase in genes involved in redox-sensitive transcription (nuclear factor erythroid 2-like 2, Nfe2l2), lipid metabolism (hydroxyacyl-CoA dehydrogenase (Hadh), phospholipases C gamma 2 (Plcg2) and D1 (Plcd1)), cholesterol homeostasis and trafficking (apolipoprotein A1 (Apoa1) and ATP-binding cassette sub-family A member7 (Abca7)), inflammation (complement component 4A (C4a)), amyloid processing (N-acylaminoacyl-peptide hydrolase (Apeh)), and apoptosis (caspase 8 (Casp8) and clusterin (Clu)).
Formal Description Interaction-ID: 132531	process menopause transition increases_expression of gene/protein NFE2L2 in 9‚Äď10 month regular cyclers; compared to 6-month cyclers, involved in redox-sensitive transcription

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant decline in the expression of genes involved in molecule transport (heat shock 60 kDa protein 1 (HSPD1) and Bcl2/adenovirus E1B interacting protein 1 (Bnip1)); mitochondrial redox enzymes glutaredoxin 2 (Glrx2) and peroxiredoxin 3 (Prx3); the glutamate decarboxylases (Gad1 and Gad2, which generate the neurotransmitter GABA), and a neuronal survival gene (chemokine receptor Cxrcr4).
Formal Description Interaction-ID: 132532	process menopause transition decreases_expression of gene/protein GLRX2 in 9‚Äď10 month regular cyclers; compared to 6-month cyclers
Drugbank entries	Show/Hide entries for GLRX2
Drugbank DB00143	Glutathione not specified GLRX2
Drugbank DB00143	Glutathione not specified GLRX2

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant decline in the expression of genes involved in molecule transport (heat shock 60 kDa protein 1 (HSPD1) and Bcl2/adenovirus E1B interacting protein 1 (Bnip1)); mitochondrial redox enzymes glutaredoxin 2 (Glrx2) and peroxiredoxin 3 (Prx3); the glutamate decarboxylases (Gad1 and Gad2, which generate the neurotransmitter GABA), and a neuronal survival gene (chemokine receptor Cxrcr4).
Formal Description Interaction-ID: 132533	process menopause transition decreases_expression of gene/protein PRDX3 in 9‚Äď10 month regular cyclers; compared to 6-month cyclers

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant decline in the expression of genes involved in molecule transport (heat shock 60 kDa protein 1 (HSPD1) and Bcl2/adenovirus E1B interacting protein 1 (Bnip1)); mitochondrial redox enzymes glutaredoxin 2 (Glrx2) and peroxiredoxin 3 (Prx3); the glutamate decarboxylases (Gad1 and Gad2, which generate the neurotransmitter GABA), and a neuronal survival gene (chemokine receptor Cxrcr4).
Formal Description Interaction-ID: 132534	process menopause transition decreases_expression of gene/protein GAD1 in 9‚Äď10 month regular cyclers; compared to 6-month cyclers
Drugbank entries	Show/Hide entries for GAD1
Drugbank DB00114	Pyridoxal Phosphate cofactor GAD1
Drugbank DB00114	Pyridoxal Phosphate cofactor GAD1
Drugbank DB00114	Pyridoxal Phosphate cofactor GAD1
Drugbank DB00142	L-Glutamic Acid not specified GAD1
Drugbank DB00142	L-Glutamic Acid not specified GAD1

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant decline in the expression of genes involved in molecule transport (heat shock 60 kDa protein 1 (HSPD1) and Bcl2/adenovirus E1B interacting protein 1 (Bnip1)); mitochondrial redox enzymes glutaredoxin 2 (Glrx2) and peroxiredoxin 3 (Prx3); the glutamate decarboxylases (Gad1 and Gad2, which generate the neurotransmitter GABA), and a neuronal survival gene (chemokine receptor Cxrcr4).
Formal Description Interaction-ID: 132535	process menopause transition decreases_expression of gene/protein GAD2 in 9‚Äď10 month regular cyclers; compared to 6-month cyclers
Drugbank entries	Show/Hide entries for GAD2
Drugbank DB00114	Pyridoxal Phosphate cofactor GAD2
Drugbank DB00142	L-Glutamic Acid not specified GAD2
Drugbank DB00142	L-Glutamic Acid not specified GAD2

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant decline in the expression of genes involved in molecule transport (heat shock 60 kDa protein 1 (HSPD1) and Bcl2/adenovirus E1B interacting protein 1 (Bnip1)); mitochondrial redox enzymes glutaredoxin 2 (Glrx2) and peroxiredoxin 3 (Prx3); the glutamate decarboxylases (Gad1 and Gad2, which generate the neurotransmitter GABA), and a neuronal survival gene (chemokine receptor Cxrcr4).
Formal Description Interaction-ID: 132536	gene/protein GAD1 increases_quantity of drug/chemical compound GABA
Drugbank entries	Show/Hide entries for GAD1
Drugbank DB00114	Pyridoxal Phosphate cofactor GAD1
Drugbank DB00114	Pyridoxal Phosphate cofactor GAD1
Drugbank DB00114	Pyridoxal Phosphate cofactor GAD1
Drugbank DB00142	L-Glutamic Acid not specified GAD1
Drugbank DB00142	L-Glutamic Acid not specified GAD1

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant decline in the expression of genes involved in molecule transport (heat shock 60 kDa protein 1 (HSPD1) and Bcl2/adenovirus E1B interacting protein 1 (Bnip1)); mitochondrial redox enzymes glutaredoxin 2 (Glrx2) and peroxiredoxin 3 (Prx3); the glutamate decarboxylases (Gad1 and Gad2, which generate the neurotransmitter GABA), and a neuronal survival gene (chemokine receptor Cxrcr4).
Formal Description Interaction-ID: 132537	gene/protein GAD2 increases_quantity of drug/chemical compound GABA
Drugbank entries	Show/Hide entries for GAD2
Drugbank DB00114	Pyridoxal Phosphate cofactor GAD2
Drugbank DB00142	L-Glutamic Acid not specified GAD2
Drugbank DB00142	L-Glutamic Acid not specified GAD2

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant decline in the expression of genes involved in molecule transport (heat shock 60 kDa protein 1 (HSPD1) and Bcl2/adenovirus E1B interacting protein 1 (Bnip1)); mitochondrial redox enzymes glutaredoxin 2 (Glrx2) and peroxiredoxin 3 (Prx3); the glutamate decarboxylases (Gad1 and Gad2, which generate the neurotransmitter GABA), and a neuronal survival gene (chemokine receptor Cxrcr4).
Formal Description Interaction-ID: 132538	process menopause transition decreases_expression of gene/protein CXCR4 in 9‚Äď10 month regular cyclers; a neuronal survival gene, compared to 6-month cyclers
Drugbank entries	Show/Hide entries for CXCR4
Drugbank DB00452	Framycetin antagonist CXCR4
Drugbank DB06809	Plerixafor antagonist CXCR4

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant increase in genes involved in redox-sensitive transcription (nuclear factor erythroid 2-like 2, Nfe2l2), lipid metabolism (hydroxyacyl-CoA dehydrogenase (Hadh), phospholipases C gamma 2 (Plcg2) and D1 (Plcd1)), cholesterol homeostasis and trafficking (apolipoprotein A1 (Apoa1) and ATP-binding cassette sub-family A member7 (Abca7)), inflammation (complement component 4A (C4a)), amyloid processing (N-acylaminoacyl-peptide hydrolase (Apeh)), and apoptosis (caspase 8 (Casp8) and clusterin (Clu)).
Formal Description Interaction-ID: 132578	process menopause transition increases_expression of gene/protein HADH in 9‚Äď10 month regular cyclers; compared to 6-month cyclers, involved in lipid metabolism
Drugbank entries	Show/Hide entries for HADH
Drugbank DB00157	NADH not specified HADH
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified HADH
Drugbank DB03059	Acetoacetyl-Coenzyme A not specified HADH
Drugbank DB03612	3-Hydroxybutyryl-Coenzyme A not specified HADH
Drugbank DB00157	NADH not specified HADH
Drugbank DB01907	Nicotinamide-Adenine-Dinucleotide not specified HADH
Drugbank DB03059	Acetoacetyl-Coenzyme A not specified HADH
Drugbank DB03612	3-Hydroxybutyryl-Coenzyme A not specified HADH

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant increase in genes involved in redox-sensitive transcription (nuclear factor erythroid 2-like 2, Nfe2l2), lipid metabolism (hydroxyacyl-CoA dehydrogenase (Hadh), phospholipases C gamma 2 (Plcg2) and D1 (Plcd1)), cholesterol homeostasis and trafficking (apolipoprotein A1 (Apoa1) and ATP-binding cassette sub-family A member7 (Abca7)), inflammation (complement component 4A (C4a)), amyloid processing (N-acylaminoacyl-peptide hydrolase (Apeh)), and apoptosis (caspase 8 (Casp8) and clusterin (Clu)).
Formal Description Interaction-ID: 132579	process menopause transition increases_expression of gene/protein PLCG2 in 9‚Äď10 month regular cyclers; compared to 6-month cyclers, involved in lipid metabolism

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant increase in genes involved in redox-sensitive transcription (nuclear factor erythroid 2-like 2, Nfe2l2), lipid metabolism (hydroxyacyl-CoA dehydrogenase (Hadh), phospholipases C gamma 2 (Plcg2) and D1 (Plcd1)), cholesterol homeostasis and trafficking (apolipoprotein A1 (Apoa1) and ATP-binding cassette sub-family A member7 (Abca7)), inflammation (complement component 4A (C4a)), amyloid processing (N-acylaminoacyl-peptide hydrolase (Apeh)), and apoptosis (caspase 8 (Casp8) and clusterin (Clu)).
Formal Description Interaction-ID: 132580	process menopause transition increases_expression of gene/protein PLCD1 in 9‚Äď10 month regular cyclers; compared to 6-month cyclers, involved in lipid metabolism
Drugbank entries	Show/Hide entries for PLCD1
Drugbank DB03401	D-Myo-Inositol-1,4,5-Triphosphate not specified PLCD1
Drugbank DB03956	D-Myo-Inositol-2,4,5-Trisphosphate not specified PLCD1
Drugbank DB03401	D-Myo-Inositol-1,4,5-Triphosphate not specified PLCD1
Drugbank DB03956	D-Myo-Inositol-2,4,5-Trisphosphate not specified PLCD1

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant increase in genes involved in redox-sensitive transcription (nuclear factor erythroid 2-like 2, Nfe2l2), lipid metabolism (hydroxyacyl-CoA dehydrogenase (Hadh), phospholipases C gamma 2 (Plcg2) and D1 (Plcd1)), cholesterol homeostasis and trafficking (apolipoprotein A1 (Apoa1) and ATP-binding cassette sub-family A member7 (Abca7)), inflammation (complement component 4A (C4a)), amyloid processing (N-acylaminoacyl-peptide hydrolase (Apeh)), and apoptosis (caspase 8 (Casp8) and clusterin (Clu)).
Formal Description Interaction-ID: 132581	process menopause transition increases_expression of gene/protein APOA1 in 9‚Äď10 month regular cyclers; compared to 6-month cyclers

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant increase in genes involved in redox-sensitive transcription (nuclear factor erythroid 2-like 2, Nfe2l2), lipid metabolism (hydroxyacyl-CoA dehydrogenase (Hadh), phospholipases C gamma 2 (Plcg2) and D1 (Plcd1)), cholesterol homeostasis and trafficking (apolipoprotein A1 (Apoa1) and ATP-binding cassette sub-family A member7 (Abca7)), inflammation (complement component 4A (C4a)), amyloid processing (N-acylaminoacyl-peptide hydrolase (Apeh)), and apoptosis (caspase 8 (Casp8) and clusterin (Clu)).
Formal Description Interaction-ID: 132582	process menopause transition increases_expression of gene/protein ABCA7 in 9‚Äď10 month regular cyclers; compared to 6-month cyclers

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant increase in genes involved in redox-sensitive transcription (nuclear factor erythroid 2-like 2, Nfe2l2), lipid metabolism (hydroxyacyl-CoA dehydrogenase (Hadh), phospholipases C gamma 2 (Plcg2) and D1 (Plcd1)), cholesterol homeostasis and trafficking (apolipoprotein A1 (Apoa1) and ATP-binding cassette sub-family A member7 (Abca7)), inflammation (complement component 4A (C4a)), amyloid processing (N-acylaminoacyl-peptide hydrolase (Apeh)), and apoptosis (caspase 8 (Casp8) and clusterin (Clu)).
Formal Description Interaction-ID: 132583	process menopause transition increases_expression of gene/protein C4A in 9‚Äď10 month regular cyclers; compared to 6-month cyclers, involved in inflammation
Drugbank entries	Show/Hide entries for C4A
Drugbank DB00028	Intravenous Immunoglobulin binder C4A

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant increase in genes involved in redox-sensitive transcription (nuclear factor erythroid 2-like 2, Nfe2l2), lipid metabolism (hydroxyacyl-CoA dehydrogenase (Hadh), phospholipases C gamma 2 (Plcg2) and D1 (Plcd1)), cholesterol homeostasis and trafficking (apolipoprotein A1 (Apoa1) and ATP-binding cassette sub-family A member7 (Abca7)), inflammation (complement component 4A (C4a)), amyloid processing (N-acylaminoacyl-peptide hydrolase (Apeh)), and apoptosis (caspase 8 (Casp8) and clusterin (Clu)).
Formal Description Interaction-ID: 132584	process menopause transition increases_expression of gene/protein APEH in 9‚Äď10 month regular cyclers; compared to 6-month cyclers, involved in amyloid processing

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant increase in genes involved in redox-sensitive transcription (nuclear factor erythroid 2-like 2, Nfe2l2), lipid metabolism (hydroxyacyl-CoA dehydrogenase (Hadh), phospholipases C gamma 2 (Plcg2) and D1 (Plcd1)), cholesterol homeostasis and trafficking (apolipoprotein A1 (Apoa1) and ATP-binding cassette sub-family A member7 (Abca7)), inflammation (complement component 4A (C4a)), amyloid processing (N-acylaminoacyl-peptide hydrolase (Apeh)), and apoptosis (caspase 8 (Casp8) and clusterin (Clu)).
Formal Description Interaction-ID: 132585	process menopause transition increases_expression of gene/protein CASP8 in 9‚Äď10 month regular cyclers; compared to 6-month cyclers, involved in apoptosis

Comment	The 9‚Äď10 month regular cyclers (compared to 6-month cyclers) showed a significant increase in genes involved in redox-sensitive transcription (nuclear factor erythroid 2-like 2, Nfe2l2), lipid metabolism (hydroxyacyl-CoA dehydrogenase (Hadh), phospholipases C gamma 2 (Plcg2) and D1 (Plcd1)), cholesterol homeostasis and trafficking (apolipoprotein A1 (Apoa1) and ATP-binding cassette sub-family A member7 (Abca7)), inflammation (complement component 4A (C4a)), amyloid processing (N-acylaminoacyl-peptide hydrolase (Apeh)), and apoptosis (caspase 8 (Casp8) and clusterin (Clu)).
Formal Description Interaction-ID: 132586	process menopause transition increases_expression of gene/protein CLU in 9‚Äď10 month regular cyclers; compared to 6-month cyclers, involved in apoptosis

Comment	The pattern of serum and cortical levels of E2 across all groups differed inasmuch as serum E2 was not correlated with cortex E2 at the same endocrine stage. While serum E2 levels were highest in the 9‚Äď10 month regular and irregular cyclers and declined thereafter, the most robust E2 change was a collapse in cortex levels from 6 month to 9‚Äď10 month rats with negligible brain E2 observed in acyclic rats.
Formal Description Interaction-ID: 132622	process menopause transition increases_quantity of drug/chemical compound Estradiol in serum of the 9‚Äď10 month regular and irregular cyclers ; serum E2 was not correlated with cortex E2 at the same endocrine stage
Drugbank entries	Show/Hide entries for
Drugbank DB00783	Estradiol agonist ESR1
Drugbank DB00783	Estradiol not specified NR1I2
Drugbank DB00783	Estradiol agonist ESR2

Comment	In contrast to E2, serum P4 levels were correlated with cortical levels. In serum, P4 level was greatest in the 9‚Äď10 month irregular cyclers and declined significantly with the transition into 9‚Äď10 month acyclic, and remained low in the 16 month acyclic group. In cortex, there was a trend towards decreased P4 level from 6 month regular to 9‚Äď10 month regular and irregular cyclers, which was statistically significant when animals transitioned into acyclicity at the same age.
Formal Description Interaction-ID: 132623	process menopause transition increases_quantity of drug/chemical compound Progesterone in serum of the 9‚Äď10 month irregular cyclers; serum P4 levels were correlated with cortical levels
Drugbank entries	Show/Hide entries for
Drugbank DB00396	Progesterone agonist PGR
Drugbank DB00396	Progesterone agonist ESR1
Drugbank DB00396	Progesterone inhibitor CYP17A1
Drugbank DB00396	Progesterone antagonist NR3C2

Comment	ERalpha expression was unaffected by either chronological or endocrine aging. Conversely, ERbeta expression declined in the 9‚Äď10 month irregular cyclers and rebounded with the onset of acyclicity at the same age.
Formal Description Interaction-ID: 132624	process aging NOT affects_expression of gene/protein ESR1
Drugbank entries	Show/Hide entries for ESR1
Drugbank DB00255	Diethylstilbestrol agonist ESR1
Drugbank DB00269	Chlorotrianisene agonist ESR1
Drugbank DB00286	Conjugated Estrogens agonist ESR1
Drugbank DB00294	Etonogestrel agonist ESR1
Drugbank DB00304	Desogestrel agonist ESR1
Drugbank DB00367	Levonorgestrel other ESR1
Drugbank DB00396	Progesterone agonist ESR1
Drugbank DB00481	Raloxifene agonist ESR1
Drugbank DB00506	Norgestrel agonist ESR1
Drugbank DB00539	Toremifene modulator ESR1
Drugbank DB00603	Medroxyprogesterone agonist ESR1
Drugbank DB00655	Estrone agonist ESR1
Drugbank DB00675	Tamoxifen antagonist ESR1
Drugbank DB00783	Estradiol agonist ESR1
Drugbank DB00823	Ethynodiol Diacetate agonist ESR1
Drugbank DB00882	Clomifene antagonist ESR1
Drugbank DB00890	Dienestrol agonist ESR1
Drugbank DB00947	Fulvestrant antagonist ESR1
Drugbank DB00957	Norgestimate agonist ESR1
Drugbank DB00977	Ethinyl Estradiol agonist ESR1
Drugbank DB01065	Melatonin antagonist ESR1
Drugbank DB01108	Trilostane allosteric modulator ESR1
Drugbank DB01183	Naloxone other/unknown ESR1
Drugbank DB01185	Fluoxymesterone antagonist ESR1
Drugbank DB01196	Estramustine agonist ESR1
Drugbank DB01357	Mestranol agonist ESR1
Drugbank DB01406	Danazol agonist ESR1
Drugbank DB01431	Allylestrenol agonist ESR1
Drugbank DB01645	Genistein not specified ESR1
Drugbank DB02615	Compound 19 not specified ESR1
Drugbank DB02715	Compound 18 not specified ESR1
Drugbank DB03742	Compound 4-D not specified ESR1
Drugbank DB03802	1-[4-(Octahydro-Pyrido[1,2-a]Pyrazin-2-Y ... not specified ESR1
Drugbank DB04471	2-Phenyl-1-[4-(2-Piperidin-1-Yl-Ethoxy)- ... not specified ESR1
Drugbank DB04573	Estriol agonist ESR1
Drugbank DB04574	Estropipate agonist ESR1
Drugbank DB04575	Quinestrol agonist ESR1
Drugbank DB06713	Norelgestromin agonist ESR1
Drugbank DB06871	17-METHYL-17-ALPHA-DIHYDROEQUILENIN not specified ESR1
Drugbank DB06898	4-(2-amino-1-methyl-1H-imidazo[4,5-b]pyr ... not specified ESR1
Drugbank DB06927	[5-HYDROXY-2-(4-HYDROXYPHENYL)-1-BENZOFU ... not specified ESR1
Drugbank DB07086	4-[(1S,2S,5S)-5-(HYDROXYMETHYL)-8-METHYL ... not specified ESR1
Drugbank DB07087	4-[(1S,2S,5S,9R)-5-(HYDROXYMETHYL)-8,9-D ... not specified ESR1
Drugbank DB07195	4-[(1S,2S,5S)-5-(HYDROXYMETHYL)-6,8,9-TR ... not specified ESR1
Drugbank DB07567	(2R,3R,4S)-3-(4-HYDROXYPHENYL)-4-METHYL- ... not specified ESR1
Drugbank DB07638	(3AS,4R,9BR)-2,2-DIFLUORO-4-(4-HYDROXYPH ... not specified ESR1
Drugbank DB07678	(9ALPHA,13BETA,17BETA)-2-[(1Z)-BUT-1-EN- ... not specified ESR1
Drugbank DB07707	(9BETA,11ALPHA,13ALPHA,14BETA,17ALPHA)-1 ... not specified ESR1
Drugbank DB07708	3-CHLORO-2-(4-HYDROXYPHENYL)-2H-INDAZOL- ... not specified ESR1
Drugbank DB07712	3-ETHYL-2-(4-HYDROXYPHENYL)-2H-INDAZOL-5 ... not specified ESR1
Drugbank DB07932	dimethyl (1R,4S)-5,6-bis(4-hydroxyphenyl ... not specified ESR1
Drugbank DB07933	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-1,2,3,3 ... not specified ESR1
Drugbank DB07991	N-[(1R)-3-(4-HYDROXYPHENYL)-1-METHYLPROP ... not specified ESR1
Drugbank DB08020	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-6-(METH ... not specified ESR1
Drugbank DB08047	4-[1-allyl-7-(trifluoromethyl)-1H-indazo ... not specified ESR1
Drugbank DB08048	4-(6-HYDROXY-1H-INDAZOL-3-YL)BENZENE-1,3 ... not specified ESR1
Drugbank DB08320	DIETHYL (1R,2S,3R,4S)-5,6-BIS(4-HYDROXYP ... not specified ESR1
Drugbank DB08398	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]P ... not specified ESR1
Drugbank DB08595	4-[(1S,2R,5S)-4,4,8-TRIMETHYL-3-OXABICYC ... not specified ESR1
Drugbank DB08737	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-1,2,3,3 ... not specified ESR1
Drugbank DB08773	RALOXIFENE CORE not specified ESR1
Drugbank DB00255	Diethylstilbestrol agonist ESR1
Drugbank DB00269	Chlorotrianisene agonist ESR1
Drugbank DB00286	Conjugated Estrogens agonist ESR1
Drugbank DB00294	Etonogestrel agonist ESR1
Drugbank DB00481	Raloxifene agonist ESR1
Drugbank DB00539	Toremifene modulator ESR1
Drugbank DB00655	Estrone agonist ESR1
Drugbank DB00882	Clomifene antagonist ESR1
Drugbank DB00890	Dienestrol agonist ESR1
Drugbank DB00947	Fulvestrant antagonist ESR1
Drugbank DB00957	Norgestimate agonist ESR1
Drugbank DB00977	Ethinyl Estradiol agonist ESR1
Drugbank DB01196	Estramustine agonist ESR1
Drugbank DB01357	Mestranol agonist ESR1
Drugbank DB02615	Compound 19 not specified ESR1
Drugbank DB02715	Compound 18 not specified ESR1
Drugbank DB03742	Compound 4-D not specified ESR1
Drugbank DB03802	1-[4-(Octahydro-Pyrido[1,2-a]Pyrazin-2-Y ... not specified ESR1
Drugbank DB04471	2-Phenyl-1-[4-(2-Piperidin-1-Yl-Ethoxy)- ... not specified ESR1
Drugbank DB04573	Estriol agonist ESR1
Drugbank DB04575	Quinestrol agonist ESR1

Comment	Compared to 6 month regular cyclers, the 9‚Äď10 month irregular cyclers had an increased expression of both PR-A and PR-B. The major difference in PR-A expression was between the 6 month- and 9‚Äď10 month regular cyclers whereas that in PR-B expression was between the 9 month regular- and irregular cyclers. The expression of PGRMC1 did not change across group.
Formal Description Interaction-ID: 132625	process menopause transition increases_expression of gene/protein PGR (isoform A) in 9‚Äď10 month irregular cyclers; compared to 6 month regular cyclers

Comment	Estrogen protects the brain against AD in part by reducing beta-amyloid production and enhancing its clearance, protecting against apoptosis, supporting neuronal function and signaling. (cited information)
Formal Description Interaction-ID: 132626	drug/chemical compound Estrogen decreases_activity of disease Alzheimer disease in AD brain; by reducing beta-amyloid production and enhancing its clearance, protecting against apoptosis, supporting neuronal function and signaling

Comment	The pattern of serum and cortical levels of E2 across all groups differed inasmuch as serum E2 was not correlated with cortex E2 at the same endocrine stage. While serum E2 levels were highest in the 9‚Äď10 month regular and irregular cyclers and declined thereafter, the most robust E2 change was a collapse in cortex levels from 6 month to 9‚Äď10 month rats with negligible brain E2 observed in acyclic rats.
Formal Description Interaction-ID: 132627	process menopause transition decreases_quantity of drug/chemical compound Estradiol in cortex of 6 month to 9‚Äď10 month rats; serum E2 was not correlated with cortex E2 at the same endocrine stage
Drugbank entries	Show/Hide entries for
Drugbank DB00783	Estradiol agonist ESR1
Drugbank DB00783	Estradiol not specified NR1I2
Drugbank DB00783	Estradiol agonist ESR2

Comment	In contrast to E2, serum P4 levels were correlated with cortical levels. In serum, P4 level was greatest in the 9‚Äď10 month irregular cyclers and declined significantly with the transition into 9‚Äď10 month acyclic, and remained low in the 16 month acyclic group. In cortex, there was a trend towards decreased P4 level from 6 month regular to 9‚Äď10 month regular and irregular cyclers, which was statistically significant when animals transitioned into acyclicity at the same age.
Formal Description Interaction-ID: 132628	process menopause transition decreases_quantity of drug/chemical compound Progesterone in serum of the transition into 9‚Äď10 month acyclic and in the cortex from 6 month regular to 9‚Äď10 month regular and irregular cyclers; serum P4 levels were correlated with cortical levels, remaining low in the 16 month acyclic group
Drugbank entries	Show/Hide entries for
Drugbank DB00396	Progesterone agonist PGR
Drugbank DB00396	Progesterone agonist ESR1
Drugbank DB00396	Progesterone inhibitor CYP17A1
Drugbank DB00396	Progesterone antagonist NR3C2

Comment	ERalpha expression was unaffected by either chronological or endocrine aging. Conversely, ERbeta expression declined in the 9‚Äď10 month irregular cyclers and rebounded with the onset of acyclicity at the same age.
Formal Description Interaction-ID: 132629	process chronological aging NOT affects_expression of gene/protein ESR1
Drugbank entries	Show/Hide entries for ESR1
Drugbank DB00255	Diethylstilbestrol agonist ESR1
Drugbank DB00269	Chlorotrianisene agonist ESR1
Drugbank DB00286	Conjugated Estrogens agonist ESR1
Drugbank DB00294	Etonogestrel agonist ESR1
Drugbank DB00304	Desogestrel agonist ESR1
Drugbank DB00367	Levonorgestrel other ESR1
Drugbank DB00396	Progesterone agonist ESR1
Drugbank DB00481	Raloxifene agonist ESR1
Drugbank DB00506	Norgestrel agonist ESR1
Drugbank DB00539	Toremifene modulator ESR1
Drugbank DB00603	Medroxyprogesterone agonist ESR1
Drugbank DB00655	Estrone agonist ESR1
Drugbank DB00675	Tamoxifen antagonist ESR1
Drugbank DB00783	Estradiol agonist ESR1
Drugbank DB00823	Ethynodiol Diacetate agonist ESR1
Drugbank DB00882	Clomifene antagonist ESR1
Drugbank DB00890	Dienestrol agonist ESR1
Drugbank DB00947	Fulvestrant antagonist ESR1
Drugbank DB00957	Norgestimate agonist ESR1
Drugbank DB00977	Ethinyl Estradiol agonist ESR1
Drugbank DB01065	Melatonin antagonist ESR1
Drugbank DB01108	Trilostane allosteric modulator ESR1
Drugbank DB01183	Naloxone other/unknown ESR1
Drugbank DB01185	Fluoxymesterone antagonist ESR1
Drugbank DB01196	Estramustine agonist ESR1
Drugbank DB01357	Mestranol agonist ESR1
Drugbank DB01406	Danazol agonist ESR1
Drugbank DB01431	Allylestrenol agonist ESR1
Drugbank DB01645	Genistein not specified ESR1
Drugbank DB02615	Compound 19 not specified ESR1
Drugbank DB02715	Compound 18 not specified ESR1
Drugbank DB03742	Compound 4-D not specified ESR1
Drugbank DB03802	1-[4-(Octahydro-Pyrido[1,2-a]Pyrazin-2-Y ... not specified ESR1
Drugbank DB04471	2-Phenyl-1-[4-(2-Piperidin-1-Yl-Ethoxy)- ... not specified ESR1
Drugbank DB04573	Estriol agonist ESR1
Drugbank DB04574	Estropipate agonist ESR1
Drugbank DB04575	Quinestrol agonist ESR1
Drugbank DB06713	Norelgestromin agonist ESR1
Drugbank DB06871	17-METHYL-17-ALPHA-DIHYDROEQUILENIN not specified ESR1
Drugbank DB06898	4-(2-amino-1-methyl-1H-imidazo[4,5-b]pyr ... not specified ESR1
Drugbank DB06927	[5-HYDROXY-2-(4-HYDROXYPHENYL)-1-BENZOFU ... not specified ESR1
Drugbank DB07086	4-[(1S,2S,5S)-5-(HYDROXYMETHYL)-8-METHYL ... not specified ESR1
Drugbank DB07087	4-[(1S,2S,5S,9R)-5-(HYDROXYMETHYL)-8,9-D ... not specified ESR1
Drugbank DB07195	4-[(1S,2S,5S)-5-(HYDROXYMETHYL)-6,8,9-TR ... not specified ESR1
Drugbank DB07567	(2R,3R,4S)-3-(4-HYDROXYPHENYL)-4-METHYL- ... not specified ESR1
Drugbank DB07638	(3AS,4R,9BR)-2,2-DIFLUORO-4-(4-HYDROXYPH ... not specified ESR1
Drugbank DB07678	(9ALPHA,13BETA,17BETA)-2-[(1Z)-BUT-1-EN- ... not specified ESR1
Drugbank DB07707	(9BETA,11ALPHA,13ALPHA,14BETA,17ALPHA)-1 ... not specified ESR1
Drugbank DB07708	3-CHLORO-2-(4-HYDROXYPHENYL)-2H-INDAZOL- ... not specified ESR1
Drugbank DB07712	3-ETHYL-2-(4-HYDROXYPHENYL)-2H-INDAZOL-5 ... not specified ESR1
Drugbank DB07932	dimethyl (1R,4S)-5,6-bis(4-hydroxyphenyl ... not specified ESR1
Drugbank DB07933	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-1,2,3,3 ... not specified ESR1
Drugbank DB07991	N-[(1R)-3-(4-HYDROXYPHENYL)-1-METHYLPROP ... not specified ESR1
Drugbank DB08020	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-6-(METH ... not specified ESR1
Drugbank DB08047	4-[1-allyl-7-(trifluoromethyl)-1H-indazo ... not specified ESR1
Drugbank DB08048	4-(6-HYDROXY-1H-INDAZOL-3-YL)BENZENE-1,3 ... not specified ESR1
Drugbank DB08320	DIETHYL (1R,2S,3R,4S)-5,6-BIS(4-HYDROXYP ... not specified ESR1
Drugbank DB08398	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]P ... not specified ESR1
Drugbank DB08595	4-[(1S,2R,5S)-4,4,8-TRIMETHYL-3-OXABICYC ... not specified ESR1
Drugbank DB08737	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-1,2,3,3 ... not specified ESR1
Drugbank DB08773	RALOXIFENE CORE not specified ESR1
Drugbank DB00255	Diethylstilbestrol agonist ESR1
Drugbank DB00269	Chlorotrianisene agonist ESR1
Drugbank DB00286	Conjugated Estrogens agonist ESR1
Drugbank DB00294	Etonogestrel agonist ESR1
Drugbank DB00481	Raloxifene agonist ESR1
Drugbank DB00539	Toremifene modulator ESR1
Drugbank DB00655	Estrone agonist ESR1
Drugbank DB00882	Clomifene antagonist ESR1
Drugbank DB00890	Dienestrol agonist ESR1
Drugbank DB00947	Fulvestrant antagonist ESR1
Drugbank DB00957	Norgestimate agonist ESR1
Drugbank DB00977	Ethinyl Estradiol agonist ESR1
Drugbank DB01196	Estramustine agonist ESR1
Drugbank DB01357	Mestranol agonist ESR1
Drugbank DB02615	Compound 19 not specified ESR1
Drugbank DB02715	Compound 18 not specified ESR1
Drugbank DB03742	Compound 4-D not specified ESR1
Drugbank DB03802	1-[4-(Octahydro-Pyrido[1,2-a]Pyrazin-2-Y ... not specified ESR1
Drugbank DB04471	2-Phenyl-1-[4-(2-Piperidin-1-Yl-Ethoxy)- ... not specified ESR1
Drugbank DB04573	Estriol agonist ESR1
Drugbank DB04575	Quinestrol agonist ESR1

Comment	ERalpha expression was unaffected by either chronological or endocrine aging. Conversely, ERbeta expression declined in the 9‚Äď10 month irregular cyclers and rebounded with the onset of acyclicity at the same age.
Formal Description Interaction-ID: 132630	process endocrine aging NOT affects_expression of gene/protein ESR1
Drugbank entries	Show/Hide entries for ESR1
Drugbank DB00255	Diethylstilbestrol agonist ESR1
Drugbank DB00269	Chlorotrianisene agonist ESR1
Drugbank DB00286	Conjugated Estrogens agonist ESR1
Drugbank DB00294	Etonogestrel agonist ESR1
Drugbank DB00304	Desogestrel agonist ESR1
Drugbank DB00367	Levonorgestrel other ESR1
Drugbank DB00396	Progesterone agonist ESR1
Drugbank DB00481	Raloxifene agonist ESR1
Drugbank DB00506	Norgestrel agonist ESR1
Drugbank DB00539	Toremifene modulator ESR1
Drugbank DB00603	Medroxyprogesterone agonist ESR1
Drugbank DB00655	Estrone agonist ESR1
Drugbank DB00675	Tamoxifen antagonist ESR1
Drugbank DB00783	Estradiol agonist ESR1
Drugbank DB00823	Ethynodiol Diacetate agonist ESR1
Drugbank DB00882	Clomifene antagonist ESR1
Drugbank DB00890	Dienestrol agonist ESR1
Drugbank DB00947	Fulvestrant antagonist ESR1
Drugbank DB00957	Norgestimate agonist ESR1
Drugbank DB00977	Ethinyl Estradiol agonist ESR1
Drugbank DB01065	Melatonin antagonist ESR1
Drugbank DB01108	Trilostane allosteric modulator ESR1
Drugbank DB01183	Naloxone other/unknown ESR1
Drugbank DB01185	Fluoxymesterone antagonist ESR1
Drugbank DB01196	Estramustine agonist ESR1
Drugbank DB01357	Mestranol agonist ESR1
Drugbank DB01406	Danazol agonist ESR1
Drugbank DB01431	Allylestrenol agonist ESR1
Drugbank DB01645	Genistein not specified ESR1
Drugbank DB02615	Compound 19 not specified ESR1
Drugbank DB02715	Compound 18 not specified ESR1
Drugbank DB03742	Compound 4-D not specified ESR1
Drugbank DB03802	1-[4-(Octahydro-Pyrido[1,2-a]Pyrazin-2-Y ... not specified ESR1
Drugbank DB04471	2-Phenyl-1-[4-(2-Piperidin-1-Yl-Ethoxy)- ... not specified ESR1
Drugbank DB04573	Estriol agonist ESR1
Drugbank DB04574	Estropipate agonist ESR1
Drugbank DB04575	Quinestrol agonist ESR1
Drugbank DB06713	Norelgestromin agonist ESR1
Drugbank DB06871	17-METHYL-17-ALPHA-DIHYDROEQUILENIN not specified ESR1
Drugbank DB06898	4-(2-amino-1-methyl-1H-imidazo[4,5-b]pyr ... not specified ESR1
Drugbank DB06927	[5-HYDROXY-2-(4-HYDROXYPHENYL)-1-BENZOFU ... not specified ESR1
Drugbank DB07086	4-[(1S,2S,5S)-5-(HYDROXYMETHYL)-8-METHYL ... not specified ESR1
Drugbank DB07087	4-[(1S,2S,5S,9R)-5-(HYDROXYMETHYL)-8,9-D ... not specified ESR1
Drugbank DB07195	4-[(1S,2S,5S)-5-(HYDROXYMETHYL)-6,8,9-TR ... not specified ESR1
Drugbank DB07567	(2R,3R,4S)-3-(4-HYDROXYPHENYL)-4-METHYL- ... not specified ESR1
Drugbank DB07638	(3AS,4R,9BR)-2,2-DIFLUORO-4-(4-HYDROXYPH ... not specified ESR1
Drugbank DB07678	(9ALPHA,13BETA,17BETA)-2-[(1Z)-BUT-1-EN- ... not specified ESR1
Drugbank DB07707	(9BETA,11ALPHA,13ALPHA,14BETA,17ALPHA)-1 ... not specified ESR1
Drugbank DB07708	3-CHLORO-2-(4-HYDROXYPHENYL)-2H-INDAZOL- ... not specified ESR1
Drugbank DB07712	3-ETHYL-2-(4-HYDROXYPHENYL)-2H-INDAZOL-5 ... not specified ESR1
Drugbank DB07932	dimethyl (1R,4S)-5,6-bis(4-hydroxyphenyl ... not specified ESR1
Drugbank DB07933	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-1,2,3,3 ... not specified ESR1
Drugbank DB07991	N-[(1R)-3-(4-HYDROXYPHENYL)-1-METHYLPROP ... not specified ESR1
Drugbank DB08020	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-6-(METH ... not specified ESR1
Drugbank DB08047	4-[1-allyl-7-(trifluoromethyl)-1H-indazo ... not specified ESR1
Drugbank DB08048	4-(6-HYDROXY-1H-INDAZOL-3-YL)BENZENE-1,3 ... not specified ESR1
Drugbank DB08320	DIETHYL (1R,2S,3R,4S)-5,6-BIS(4-HYDROXYP ... not specified ESR1
Drugbank DB08398	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]P ... not specified ESR1
Drugbank DB08595	4-[(1S,2R,5S)-4,4,8-TRIMETHYL-3-OXABICYC ... not specified ESR1
Drugbank DB08737	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-1,2,3,3 ... not specified ESR1
Drugbank DB08773	RALOXIFENE CORE not specified ESR1
Drugbank DB00255	Diethylstilbestrol agonist ESR1
Drugbank DB00269	Chlorotrianisene agonist ESR1
Drugbank DB00286	Conjugated Estrogens agonist ESR1
Drugbank DB00294	Etonogestrel agonist ESR1
Drugbank DB00481	Raloxifene agonist ESR1
Drugbank DB00539	Toremifene modulator ESR1
Drugbank DB00655	Estrone agonist ESR1
Drugbank DB00882	Clomifene antagonist ESR1
Drugbank DB00890	Dienestrol agonist ESR1
Drugbank DB00947	Fulvestrant antagonist ESR1
Drugbank DB00957	Norgestimate agonist ESR1
Drugbank DB00977	Ethinyl Estradiol agonist ESR1
Drugbank DB01196	Estramustine agonist ESR1
Drugbank DB01357	Mestranol agonist ESR1
Drugbank DB02615	Compound 19 not specified ESR1
Drugbank DB02715	Compound 18 not specified ESR1
Drugbank DB03742	Compound 4-D not specified ESR1
Drugbank DB03802	1-[4-(Octahydro-Pyrido[1,2-a]Pyrazin-2-Y ... not specified ESR1
Drugbank DB04471	2-Phenyl-1-[4-(2-Piperidin-1-Yl-Ethoxy)- ... not specified ESR1
Drugbank DB04573	Estriol agonist ESR1
Drugbank DB04575	Quinestrol agonist ESR1

Comment	ERalpha expression was unaffected by either chronological or endocrine aging. Conversely, ERbeta expression declined in the 9‚Äď10 month irregular cyclers and rebounded with the onset of acyclicity at the same age.
Formal Description Interaction-ID: 132631	process menopause transition decreases_expression of gene/protein ESR2 in the 9‚Äď10 month irregular cyclers
Drugbank entries	Show/Hide entries for ESR2
Drugbank DB00255	Diethylstilbestrol agonist ESR2
Drugbank DB00481	Raloxifene agonist ESR2
Drugbank DB00675	Tamoxifen agonist ESR2
Drugbank DB00783	Estradiol agonist ESR2
Drugbank DB01108	Trilostane allosteric modulator ESR2
Drugbank DB01196	Estramustine other/unknown ESR2
Drugbank DB01645	Genistein not specified ESR2
Drugbank DB02983	Para-Mercury-Benzenesulfonic Acid not specified ESR2
Drugbank DB03860	N-Butyl-11-[(7r,8r,9s,13s,14s,17s)-3,17- ... not specified ESR2
Drugbank DB03882	5-Alpha-Androstane-3-Beta,17beta-Diol agonist ESR2
Drugbank DB04020	4-(2-{[4-{[3-(4-Chlorophenyl)Propyl]Sulf ... not specified ESR2
Drugbank DB04573	Estriol agonist ESR2
Drugbank DB04574	Estropipate agonist ESR2
Drugbank DB06832	2-(3-FLUORO-4-HYDROXYPHENYL)-7-VINYL-1,3 ... not specified ESR2
Drugbank DB06875	3-(3-FLUORO-4-HYDROXYPHENYL)-7-HYDROXY-1 ... not specified ESR2
Drugbank DB06927	[5-HYDROXY-2-(4-HYDROXYPHENYL)-1-BENZOFU ... not specified ESR2
Drugbank DB06937	4-(6-HYDROXY-BENZO[D]ISOXAZOL-3-YL)BENZE ... not specified ESR2
Drugbank DB07009	2-(5-HYDROXY-NAPHTHALEN-1-YL)-1,3-BENZOO ... not specified ESR2
Drugbank DB07032	2-(4-HYDROXY-PHENYL)BENZOFURAN-5-OL not specified ESR2
Drugbank DB07036	(3aS,4R,9bR)-2,2-difluoro-4-(4-hydroxyph ... not specified ESR2
Drugbank DB07119	1-CHLORO-6-(4-HYDROXYPHENYL)-2-NAPHTHOL not specified ESR2
Drugbank DB07150	4-(4-HYDROXYPHENYL)-1-NAPHTHALDEHYDE OXI ... not specified ESR2
Drugbank DB07198	5-HYDROXY-2-(4-HYDROXYPHENYL)-1-BENZOFUR ... not specified ESR2
Drugbank DB07230	3-BROMO-6-HYDROXY-2-(4-HYDROXYPHENYL)-1H ... not specified ESR2
Drugbank DB07236	3-(6-HYDROXY-NAPHTHALEN-2-YL)-BENZO[D]IS ... not specified ESR2
Drugbank DB07638	(3AS,4R,9BR)-2,2-DIFLUORO-4-(4-HYDROXYPH ... not specified ESR2
Drugbank DB07702	(16ALPHA,17ALPHA)-ESTRA-1,3,5(10)-TRIENE ... not specified ESR2
Drugbank DB07757	(9aS)-4-bromo-9a-butyl-7-hydroxy-1,2,9,9 ... not specified ESR2
Drugbank DB07933	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-1,2,3,3 ... not specified ESR2
Drugbank DB08020	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-6-(METH ... not specified ESR2
Drugbank DB00481	Raloxifene agonist ESR2
Drugbank DB01196	Estramustine other/unknown ESR2
Drugbank DB01645	Genistein not specified ESR2
Drugbank DB02983	Para-Mercury-Benzenesulfonic Acid not specified ESR2
Drugbank DB03860	N-Butyl-11-[(7r,8r,9s,13s,14s,17s)-3,17- ... not specified ESR2
Drugbank DB04020	4-(2-{[4-{[3-(4-Chlorophenyl)Propyl]Sulf ... not specified ESR2

Comment	ERalpha expression was unaffected by either chronological or endocrine aging. Conversely, ERbeta expression declined in the 9‚Äď10 month irregular cyclers and rebounded with the onset of acyclicity at the same age.
Formal Description Interaction-ID: 132632	phenotype acyclicity increases_expression of gene/protein ESR2 in the 9‚Äď10 month irregular cyclers
Drugbank entries	Show/Hide entries for ESR2
Drugbank DB00255	Diethylstilbestrol agonist ESR2
Drugbank DB00481	Raloxifene agonist ESR2
Drugbank DB00675	Tamoxifen agonist ESR2
Drugbank DB00783	Estradiol agonist ESR2
Drugbank DB01108	Trilostane allosteric modulator ESR2
Drugbank DB01196	Estramustine other/unknown ESR2
Drugbank DB01645	Genistein not specified ESR2
Drugbank DB02983	Para-Mercury-Benzenesulfonic Acid not specified ESR2
Drugbank DB03860	N-Butyl-11-[(7r,8r,9s,13s,14s,17s)-3,17- ... not specified ESR2
Drugbank DB03882	5-Alpha-Androstane-3-Beta,17beta-Diol agonist ESR2
Drugbank DB04020	4-(2-{[4-{[3-(4-Chlorophenyl)Propyl]Sulf ... not specified ESR2
Drugbank DB04573	Estriol agonist ESR2
Drugbank DB04574	Estropipate agonist ESR2
Drugbank DB06832	2-(3-FLUORO-4-HYDROXYPHENYL)-7-VINYL-1,3 ... not specified ESR2
Drugbank DB06875	3-(3-FLUORO-4-HYDROXYPHENYL)-7-HYDROXY-1 ... not specified ESR2
Drugbank DB06927	[5-HYDROXY-2-(4-HYDROXYPHENYL)-1-BENZOFU ... not specified ESR2
Drugbank DB06937	4-(6-HYDROXY-BENZO[D]ISOXAZOL-3-YL)BENZE ... not specified ESR2
Drugbank DB07009	2-(5-HYDROXY-NAPHTHALEN-1-YL)-1,3-BENZOO ... not specified ESR2
Drugbank DB07032	2-(4-HYDROXY-PHENYL)BENZOFURAN-5-OL not specified ESR2
Drugbank DB07036	(3aS,4R,9bR)-2,2-difluoro-4-(4-hydroxyph ... not specified ESR2
Drugbank DB07119	1-CHLORO-6-(4-HYDROXYPHENYL)-2-NAPHTHOL not specified ESR2
Drugbank DB07150	4-(4-HYDROXYPHENYL)-1-NAPHTHALDEHYDE OXI ... not specified ESR2
Drugbank DB07198	5-HYDROXY-2-(4-HYDROXYPHENYL)-1-BENZOFUR ... not specified ESR2
Drugbank DB07230	3-BROMO-6-HYDROXY-2-(4-HYDROXYPHENYL)-1H ... not specified ESR2
Drugbank DB07236	3-(6-HYDROXY-NAPHTHALEN-2-YL)-BENZO[D]IS ... not specified ESR2
Drugbank DB07638	(3AS,4R,9BR)-2,2-DIFLUORO-4-(4-HYDROXYPH ... not specified ESR2
Drugbank DB07702	(16ALPHA,17ALPHA)-ESTRA-1,3,5(10)-TRIENE ... not specified ESR2
Drugbank DB07757	(9aS)-4-bromo-9a-butyl-7-hydroxy-1,2,9,9 ... not specified ESR2
Drugbank DB07933	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-1,2,3,3 ... not specified ESR2
Drugbank DB08020	(3AS,4R,9BR)-4-(4-HYDROXYPHENYL)-6-(METH ... not specified ESR2
Drugbank DB00481	Raloxifene agonist ESR2
Drugbank DB01196	Estramustine other/unknown ESR2
Drugbank DB01645	Genistein not specified ESR2
Drugbank DB02983	Para-Mercury-Benzenesulfonic Acid not specified ESR2
Drugbank DB03860	N-Butyl-11-[(7r,8r,9s,13s,14s,17s)-3,17- ... not specified ESR2
Drugbank DB04020	4-(2-{[4-{[3-(4-Chlorophenyl)Propyl]Sulf ... not specified ESR2

Comment	In contrast to E2, serum P4 levels were correlated with cortical levels. In serum, P4 level was greatest in the 9‚Äď10 month irregular cyclers and declined significantly with the transition into 9‚Äď10 month acyclic, and remained low in the 16 month acyclic group. In cortex, there was a trend towards decreased P4 level from 6 month regular to 9‚Äď10 month regular and irregular cyclers, which was statistically significant when animals transitioned into acyclicity at the same age.
Formal Description Interaction-ID: 132633	phenotype acyclicity decreases_quantity of drug/chemical compound Progesterone in the cortex of female rats transitioned into acyclicity
Drugbank entries	Show/Hide entries for
Drugbank DB00396	Progesterone agonist PGR
Drugbank DB00396	Progesterone agonist ESR1
Drugbank DB00396	Progesterone inhibitor CYP17A1
Drugbank DB00396	Progesterone antagonist NR3C2

Comment	Compared to 6 month regular cyclers, the 9‚Äď10 month irregular cyclers had an increased expression of both PR-A and PR-B. The major difference in PR-A expression was between the 6 month- and 9‚Äď10 month regular cyclers whereas that in PR-B expression was between the 9 month regular- and irregular cyclers. The expression of PGRMC1 did not change across group.
Formal Description Interaction-ID: 132634	process menopause transition increases_expression of gene/protein PGR (isoform B) in 9‚Äď10 month irregular cyclers; compared to 6 month regular cyclers

Comment	Compared to 6 month regular cyclers, the 9‚Äď10 month irregular cyclers had an increased expression of both PR-A and PR-B. The major difference in PR-A expression was between the 6 month- and 9‚Äď10 month regular cyclers whereas that in PR-B expression was between the 9 month regular- and irregular cyclers. The expression of PGRMC1 did not change across group.
Formal Description Interaction-ID: 132635	process menopause transition NOT affects_expression of gene/protein PGRMC1 in all compared groups of the Perimenopause Animal Model (PAM)

Comment	Compared to 6 month regular cyclers, the 9‚Äď10 month irregular cyclers had an increased expression of both PR-A and PR-B. The major difference in PR-A expression was between the 6 month- and 9‚Äď10 month regular cyclers whereas that in PR-B expression was between the 9 month regular- and irregular cyclers. The expression of PGRMC1 did not change across group.
Formal Description Interaction-ID: 132636	process menopause transition increases_expression of gene/protein PGR in 9‚Äď10 month irregular cyclers; compared to 6 month regular cyclers, concerning both isoforms A and B
Drugbank entries	Show/Hide entries for PGR
Drugbank DB00294	Etonogestrel agonist PGR
Drugbank DB00304	Desogestrel agonist PGR
Drugbank DB00351	Megestrol agonist PGR
Drugbank DB00367	Levonorgestrel binder PGR
Drugbank DB00378	Dydrogesterone agonist PGR
Drugbank DB00396	Progesterone agonist PGR
Drugbank DB00506	Norgestrel agonist PGR
Drugbank DB00588	Fluticasone Propionate agonist PGR
Drugbank DB00603	Medroxyprogesterone agonist PGR
Drugbank DB00717	Norethindrone agonist PGR
Drugbank DB00823	Ethynodiol Diacetate agonist PGR
Drugbank DB00834	Mifepristone antagonist PGR
Drugbank DB00957	Norgestimate agonist PGR
Drugbank DB01395	Drospirenone agonist PGR
Drugbank DB01406	Danazol agonist PGR
Drugbank DB01431	Allylestrenol agonist PGR
Drugbank DB02998	Methyltrienolone not specified PGR
Drugbank DB04787	Tanaproget not specified PGR
Drugbank DB06713	Norelgestromin agonist PGR
Drugbank DB00294	Etonogestrel agonist PGR
Drugbank DB00351	Megestrol agonist PGR
Drugbank DB00378	Dydrogesterone agonist PGR
Drugbank DB00717	Norethindrone agonist PGR
Drugbank DB00957	Norgestimate agonist PGR
Drugbank DB01395	Drospirenone agonist PGR
Drugbank DB02998	Methyltrienolone not specified PGR
Drugbank DB04787	Tanaproget not specified PGR

Comment	Comparisons among 9‚Äď10 month regular cyclers, irregular cyclers, and acyclic animals represent the impact of endocrine status independent of chronological age. Compared to regular cyclers, the irregular cyclers exhibited a significant decline in the expression of genes involved in bioenergetics (ATP synthase F1 complex assembly factor 2 (Atpaf2) and estrogen-related receptor alpha (Esrra, a regulator of mitochondrial biogenesis)), lipid metabolism (phospholipase C, beta 3 (Plcb3)), inflammation (interleukin 1 receptor-like 1 (Il1rl1), the downstream Mapk3 (Erk1) and nuclear factor of kappa light polypeptide gene enhancer in B-Cells 2 (Nfkb2)), and amyloid processing (thimet oligopeptidase (Thop1) and microtubule-associated protein 2 (Map2)).
Formal Description Interaction-ID: 132639	phenotype irregular cycling decreases_expression of gene/protein ATPAF2 gene involved in bioenergetics, compared to regular cyclers

Comment	Comparisons among 9‚Äď10 month regular cyclers, irregular cyclers, and acyclic animals represent the impact of endocrine status independent of chronological age. Compared to regular cyclers, the irregular cyclers exhibited a significant decline in the expression of genes involved in bioenergetics (ATP synthase F1 complex assembly factor 2 (Atpaf2) and estrogen-related receptor alpha (Esrra, a regulator of mitochondrial biogenesis)), lipid metabolism (phospholipase C, beta 3 (Plcb3)), inflammation (interleukin 1 receptor-like 1 (Il1rl1), the downstream Mapk3 (Erk1) and nuclear factor of kappa light polypeptide gene enhancer in B-Cells 2 (Nfkb2)), and amyloid processing (thimet oligopeptidase (Thop1) and microtubule-associated protein 2 (Map2)).
Formal Description Interaction-ID: 132640	phenotype irregular cycling decreases_expression of gene/protein ESRRA regulator of mitochondrial biogenesis, compared to regular cyclers
Drugbank entries	Show/Hide entries for ESRRA
Drugbank DB00197	Troglitazone inverse agonist ESRRA
Drugbank DB06833	1-CYCLOHEXYL-N-{[1-(4-METHYLPHENYL)-1H-I ... not specified ESRRA

Comment	Comparisons among 9‚Äď10 month regular cyclers, irregular cyclers, and acyclic animals represent the impact of endocrine status independent of chronological age. Compared to regular cyclers, the irregular cyclers exhibited a significant decline in the expression of genes involved in bioenergetics (ATP synthase F1 complex assembly factor 2 (Atpaf2) and estrogen-related receptor alpha (Esrra, a regulator of mitochondrial biogenesis)), lipid metabolism (phospholipase C, beta 3 (Plcb3)), inflammation (interleukin 1 receptor-like 1 (Il1rl1), the downstream Mapk3 (Erk1) and nuclear factor of kappa light polypeptide gene enhancer in B-Cells 2 (Nfkb2)), and amyloid processing (thimet oligopeptidase (Thop1) and microtubule-associated protein 2 (Map2)).
Formal Description Interaction-ID: 132641	phenotype irregular cycling decreases_expression of gene/protein NFKB2 compared to regular cyclers
Drugbank entries	Show/Hide entries for NFKB2
Drugbank DB01296	Glucosamine antagonist NFKB2

Comment	Comparisons among 9‚Äď10 month regular cyclers, irregular cyclers, and acyclic animals represent the impact of endocrine status independent of chronological age. Compared to regular cyclers, the irregular cyclers exhibited a significant decline in the expression of genes involved in bioenergetics (ATP synthase F1 complex assembly factor 2 (Atpaf2) and estrogen-related receptor alpha (Esrra, a regulator of mitochondrial biogenesis)), lipid metabolism (phospholipase C, beta 3 (Plcb3)), inflammation (interleukin 1 receptor-like 1 (Il1rl1), the downstream Mapk3 (Erk1) and nuclear factor of kappa light polypeptide gene enhancer in B-Cells 2 (Nfkb2)), and amyloid processing (thimet oligopeptidase (Thop1) and microtubule-associated protein 2 (Map2)).
Formal Description Interaction-ID: 132642	phenotype irregular cycling decreases_expression of gene/protein PLCB3 gene involved in lipid metabolism, compared to regular cyclers

Comment	Comparisons among 9‚Äď10 month regular cyclers, irregular cyclers, and acyclic animals represent the impact of endocrine status independent of chronological age. Compared to regular cyclers, the irregular cyclers exhibited a significant decline in the expression of genes involved in bioenergetics (ATP synthase F1 complex assembly factor 2 (Atpaf2) and estrogen-related receptor alpha (Esrra, a regulator of mitochondrial biogenesis)), lipid metabolism (phospholipase C, beta 3 (Plcb3)), inflammation (interleukin 1 receptor-like 1 (Il1rl1), the downstream Mapk3 (Erk1) and nuclear factor of kappa light polypeptide gene enhancer in B-Cells 2 (Nfkb2)), and amyloid processing (thimet oligopeptidase (Thop1) and microtubule-associated protein 2 (Map2)).
Formal Description Interaction-ID: 132643	phenotype irregular cycling decreases_expression of gene/protein IL1RL1 gene involved in inflammation, compared to regular cyclers

Comment	Comparisons among 9‚Äď10 month regular cyclers, irregular cyclers, and acyclic animals represent the impact of endocrine status independent of chronological age. Compared to regular cyclers, the irregular cyclers exhibited a significant decline in the expression of genes involved in bioenergetics (ATP synthase F1 complex assembly factor 2 (Atpaf2) and estrogen-related receptor alpha (Esrra, a regulator of mitochondrial biogenesis)), lipid metabolism (phospholipase C, beta 3 (Plcb3)), inflammation (interleukin 1 receptor-like 1 (Il1rl1), the downstream Mapk3 (Erk1) and nuclear factor of kappa light polypeptide gene enhancer in B-Cells 2 (Nfkb2)), and amyloid processing (thimet oligopeptidase (Thop1) and microtubule-associated protein 2 (Map2)).
Formal Description Interaction-ID: 132644	phenotype irregular cycling decreases_expression of gene/protein MAPK3 compared to regular cyclers
Drugbank entries	Show/Hide entries for MAPK3
Drugbank DB00605	Sulindac inhibitor MAPK3
Drugbank DB01169	Arsenic trioxide inducer MAPK3
Drugbank DB02733	Purvalanol inhibitor MAPK3
Drugbank DB04604	5-iodotubercidin not specified MAPK3
Drugbank DB02733	Purvalanol inhibitor MAPK3

Comment	Comparisons among 9‚Äď10 month regular cyclers, irregular cyclers, and acyclic animals represent the impact of endocrine status independent of chronological age. Compared to regular cyclers, the irregular cyclers exhibited a significant decline in the expression of genes involved in bioenergetics (ATP synthase F1 complex assembly factor 2 (Atpaf2) and estrogen-related receptor alpha (Esrra, a regulator of mitochondrial biogenesis)), lipid metabolism (phospholipase C, beta 3 (Plcb3)), inflammation (interleukin 1 receptor-like 1 (Il1rl1), the downstream Mapk3 (Erk1) and nuclear factor of kappa light polypeptide gene enhancer in B-Cells 2 (Nfkb2)), and amyloid processing (thimet oligopeptidase (Thop1) and microtubule-associated protein 2 (Map2)).
Formal Description Interaction-ID: 132645	phenotype irregular cycling decreases_expression of gene/protein THOP1 gene involved in amyloid processing, compared to regular cyclers

Comment	Comparisons among 9‚Äď10 month regular cyclers, irregular cyclers, and acyclic animals represent the impact of endocrine status independent of chronological age. Compared to regular cyclers, the irregular cyclers exhibited a significant decline in the expression of genes involved in bioenergetics (ATP synthase F1 complex assembly factor 2 (Atpaf2) and estrogen-related receptor alpha (Esrra, a regulator of mitochondrial biogenesis)), lipid metabolism (phospholipase C, beta 3 (Plcb3)), inflammation (interleukin 1 receptor-like 1 (Il1rl1), the downstream Mapk3 (Erk1) and nuclear factor of kappa light polypeptide gene enhancer in B-Cells 2 (Nfkb2)), and amyloid processing (thimet oligopeptidase (Thop1) and microtubule-associated protein 2 (Map2)).
Formal Description Interaction-ID: 132646	phenotype irregular cycling decreases_expression of gene/protein MAP2 compared to regular cyclers
Drugbank entries	Show/Hide entries for MAP2
Drugbank DB01196	Estramustine antagonist MAP2
Drugbank DB01196	Estramustine antagonist MAP2

Comment	Compared to the 9‚Äď10 month irregular cyclers, the acyclic animals exhibited higher expression of genes involved in fatty acid uptake by the mitochondria (carnitine palmitoyltransferase 2 (Cpt2) and phospholipase A2 group 2A (Pla2g2a)), mitochondrial biogenesis and ATP generation (Atpaf2 and estrogen-related receptor beta (Esrrb)), inflammation (C-X-C motif chemokine 12 (Cxcl12), Cd40, TNF-alpha-induced protein 2 (Tnfaip2)), cholesterol homeostasis (Apoa1 and steroidogenic acute regulatory (Star)), and amyloid and apoptosis related (Apba3 and Bcl2l1).
Formal Description Interaction-ID: 132647	phenotype acyclicity increases_expression of gene/protein CPT2 gene involved in fatty acid uptake by the mitochondria, compared to the 9‚Äď10 month irregular cyclers
Drugbank entries	Show/Hide entries for CPT2
Drugbank DB00583	L-Carnitine not specified CPT2
Drugbank DB01074	Perhexiline inhibitor CPT2
Drugbank DB00583	L-Carnitine not specified CPT2

Comment	The expression of APP-Binding, Family B, Member 1 (Apbb1), decreased in acyclic animals.
Formal Description Interaction-ID: 132648	phenotype acyclicity decreases_expression of gene/protein APBB1

Comment	Functional group analyses revealed a decline in irregular cyclers relative to regular cyclers in genes involved in glucose transport, glycolysis, mitochondrial energy-transducing systems (TCA cycle, electron transfer chain, oxidative phosphorylation, mitochondrial biogenesis and dynamics), cellular redox homeostasis, inflammation (adhesion, chemokines, interleukins, phospholipases), Abeta clearance and degradation, apoptosis, and synaptic plasticity.
Formal Description Interaction-ID: 132649	phenotype irregular cycling decreases_expression of gene/protein genes involved in glucose transport compared to regular cyclers

Comment	Functional group analyses between the 9‚Äď10 month irregular cyclers and acyclic animals revealed that the deficits in glycolytic genes persisted into the acyclic condition. In contrast, mitochondrial genes were increased with the transition into acyclicity and those involved in synaptic plasticity were partially recovered.
Formal Description Interaction-ID: 132650	phenotype acyclicity decreases_expression of gene/protein genes involved in glycolysis compared 9‚Äď10 month irregular cyclers, deficits in glycolytic genes persisted into the acyclic condition

Comment	Compared to the 9‚Äď10 month irregular cyclers, the acyclic animals exhibited higher expression of genes involved in fatty acid uptake by the mitochondria (carnitine palmitoyltransferase 2 (Cpt2) and phospholipase A2 group 2A (Pla2g2a)), mitochondrial biogenesis and ATP generation (Atpaf2 and estrogen-related receptor beta (Esrrb)), inflammation (C-X-C motif chemokine 12 (Cxcl12), Cd40, TNF-alpha-induced protein 2 (Tnfaip2)), cholesterol homeostasis (Apoa1 and steroidogenic acute regulatory (Star)), and amyloid and apoptosis related (Apba3 and Bcl2l1).
Formal Description Interaction-ID: 132651	phenotype acyclicity increases_expression of gene/protein PLA2G2A gene involved in fatty acid uptake by the mitochondria, compared to the 9‚Äď10 month irregular cyclers
Drugbank entries	Show/Hide entries for PLA2G2A
Drugbank DB00328	Indomethacin inhibitor PLA2G2A
Drugbank DB00586	Diclofenac inhibitor PLA2G2A
Drugbank DB01381	Ginkgo biloba inhibitor PLA2G2A
Drugbank DB01955	1,4-Butanediol not specified PLA2G2A
Drugbank DB02080	1-{2-[2-(2-Methoxyethoxy)Ethoxy]Ethoxy}- ... not specified PLA2G2A
Drugbank DB02448	N-Tridecanoic Acid not specified PLA2G2A
Drugbank DB02504	[3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl- ... not specified PLA2G2A
Drugbank DB02936	4-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1 ... not specified PLA2G2A
Drugbank DB03121	1-Benzyl-5-Methoxy-2-Methyl-1h-Indol-3-Y ... not specified PLA2G2A
Drugbank DB03471	6-Phenyl-4(R)-(7-Phenyl-Heptanoylamino)- ... not specified PLA2G2A
Drugbank DB03784	Elaidoylamide not specified PLA2G2A
Drugbank DB04112	1-Octadecyl-2-Acetamido-2-Deoxy-Sn-Glyce ... not specified PLA2G2A
Drugbank DB04287	(S)-5-(4-Benzyloxy-Phenyl)-4-(7-Phenyl-H ... not specified PLA2G2A
Drugbank DB04786	Suramin inhibitor PLA2G2A
Drugbank DB01955	1,4-Butanediol not specified PLA2G2A
Drugbank DB02504	[3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl- ... not specified PLA2G2A
Drugbank DB02936	4-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1 ... not specified PLA2G2A
Drugbank DB03121	1-Benzyl-5-Methoxy-2-Methyl-1h-Indol-3-Y ... not specified PLA2G2A
Drugbank DB03471	6-Phenyl-4(R)-(7-Phenyl-Heptanoylamino)- ... not specified PLA2G2A
Drugbank DB03784	Elaidoylamide not specified PLA2G2A
Drugbank DB04112	1-Octadecyl-2-Acetamido-2-Deoxy-Sn-Glyce ... not specified PLA2G2A
Drugbank DB04287	(S)-5-(4-Benzyloxy-Phenyl)-4-(7-Phenyl-H ... not specified PLA2G2A

Comment	Compared to the 9‚Äď10 month irregular cyclers, the acyclic animals exhibited higher expression of genes involved in fatty acid uptake by the mitochondria (carnitine palmitoyltransferase 2 (Cpt2) and phospholipase A2 group 2A (Pla2g2a)), mitochondrial biogenesis and ATP generation (Atpaf2 and estrogen-related receptor beta (Esrrb)), inflammation (C-X-C motif chemokine 12 (Cxcl12), Cd40, TNF-alpha-induced protein 2 (Tnfaip2)), cholesterol homeostasis (Apoa1 and steroidogenic acute regulatory (Star)), and amyloid and apoptosis related (Apba3 and Bcl2l1).
Formal Description Interaction-ID: 132652	phenotype acyclicity increases_expression of gene/protein ATPAF2 gene involved in mitochondrial biogenesis and ATP generation, compared to the 9‚Äď10 month irregular cyclers

Comment	Compared to the 9‚Äď10 month irregular cyclers, the acyclic animals exhibited higher expression of genes involved in fatty acid uptake by the mitochondria (carnitine palmitoyltransferase 2 (Cpt2) and phospholipase A2 group 2A (Pla2g2a)), mitochondrial biogenesis and ATP generation (Atpaf2 and estrogen-related receptor beta (Esrrb)), inflammation (C-X-C motif chemokine 12 (Cxcl12), Cd40, TNF-alpha-induced protein 2 (Tnfaip2)), cholesterol homeostasis (Apoa1 and steroidogenic acute regulatory (Star)), and amyloid and apoptosis related (Apba3 and Bcl2l1).
Formal Description Interaction-ID: 132653	phenotype acyclicity increases_expression of gene/protein ESRRB gene involved in mitochondrial biogenesis and ATP generation, compared to the 9‚Äď10 month irregular cyclers

Comment	Compared to the 9‚Äď10 month irregular cyclers, the acyclic animals exhibited higher expression of genes involved in fatty acid uptake by the mitochondria (carnitine palmitoyltransferase 2 (Cpt2) and phospholipase A2 group 2A (Pla2g2a)), mitochondrial biogenesis and ATP generation (Atpaf2 and estrogen-related receptor beta (Esrrb)), inflammation (C-X-C motif chemokine 12 (Cxcl12), Cd40, TNF-alpha-induced protein 2 (Tnfaip2)), cholesterol homeostasis (Apoa1 and steroidogenic acute regulatory (Star)), and amyloid and apoptosis related (Apba3 and Bcl2l1).
Formal Description Interaction-ID: 132654	phenotype acyclicity increases_expression of gene/protein CXCL12 gene involved in inflammation, compared to the 9‚Äď10 month irregular cyclers
Drugbank entries	Show/Hide entries for CXCL12
Drugbank DB06822	Tinzaparin binder CXCL12

Comment	Compared to the 9‚Äď10 month irregular cyclers, the acyclic animals exhibited higher expression of genes involved in fatty acid uptake by the mitochondria (carnitine palmitoyltransferase 2 (Cpt2) and phospholipase A2 group 2A (Pla2g2a)), mitochondrial biogenesis and ATP generation (Atpaf2 and estrogen-related receptor beta (Esrrb)), inflammation (C-X-C motif chemokine 12 (Cxcl12), Cd40, TNF-alpha-induced protein 2 (Tnfaip2)), cholesterol homeostasis (Apoa1 and steroidogenic acute regulatory (Star)), and amyloid and apoptosis related (Apba3 and Bcl2l1).
Formal Description Interaction-ID: 132655	phenotype acyclicity increases_expression of gene/protein CD40 gene involved in inflammation, compared to the 9‚Äď10 month irregular cyclers

Comment	Compared to the 9‚Äď10 month irregular cyclers, the acyclic animals exhibited higher expression of genes involved in fatty acid uptake by the mitochondria (carnitine palmitoyltransferase 2 (Cpt2) and phospholipase A2 group 2A (Pla2g2a)), mitochondrial biogenesis and ATP generation (Atpaf2 and estrogen-related receptor beta (Esrrb)), inflammation (C-X-C motif chemokine 12 (Cxcl12), Cd40, TNF-alpha-induced protein 2 (Tnfaip2)), cholesterol homeostasis (Apoa1 and steroidogenic acute regulatory (Star)), and amyloid and apoptosis related (Apba3 and Bcl2l1).
Formal Description Interaction-ID: 132656	phenotype acyclicity increases_expression of gene/protein TNFAIP2 gene involved in inflammation, compared to the 9‚Äď10 month irregular cyclers

Comment	Compared to the 9‚Äď10 month irregular cyclers, the acyclic animals exhibited higher expression of genes involved in fatty acid uptake by the mitochondria (carnitine palmitoyltransferase 2 (Cpt2) and phospholipase A2 group 2A (Pla2g2a)), mitochondrial biogenesis and ATP generation (Atpaf2 and estrogen-related receptor beta (Esrrb)), inflammation (C-X-C motif chemokine 12 (Cxcl12), Cd40, TNF-alpha-induced protein 2 (Tnfaip2)), cholesterol homeostasis (Apoa1 and steroidogenic acute regulatory (Star)), and amyloid and apoptosis related (Apba3 and Bcl2l1).
Formal Description Interaction-ID: 132657	phenotype acyclicity increases_expression of gene/protein APOA1 gene involved in cholesterol homeostasis, compared to the 9‚Äď10 month irregular cyclers

Comment	Compared to the 9‚Äď10 month irregular cyclers, the acyclic animals exhibited higher expression of genes involved in fatty acid uptake by the mitochondria (carnitine palmitoyltransferase 2 (Cpt2) and phospholipase A2 group 2A (Pla2g2a)), mitochondrial biogenesis and ATP generation (Atpaf2 and estrogen-related receptor beta (Esrrb)), inflammation (C-X-C motif chemokine 12 (Cxcl12), Cd40, TNF-alpha-induced protein 2 (Tnfaip2)), cholesterol homeostasis (Apoa1 and steroidogenic acute regulatory (Star)), and amyloid and apoptosis related (Apba3 and Bcl2l1).
Formal Description Interaction-ID: 132658	phenotype acyclicity increases_expression of gene/protein STAR gene involved in cholesterol homeostasis, compared to the 9‚Äď10 month irregular cyclers

Comment	Compared to the 9‚Äď10 month irregular cyclers, the acyclic animals exhibited higher expression of genes involved in fatty acid uptake by the mitochondria (carnitine palmitoyltransferase 2 (Cpt2) and phospholipase A2 group 2A (Pla2g2a)), mitochondrial biogenesis and ATP generation (Atpaf2 and estrogen-related receptor beta (Esrrb)), inflammation (C-X-C motif chemokine 12 (Cxcl12), Cd40, TNF-alpha-induced protein 2 (Tnfaip2)), cholesterol homeostasis (Apoa1 and steroidogenic acute regulatory (Star)), and amyloid and apoptosis related (Apba3 and Bcl2l1).
Formal Description Interaction-ID: 132659	phenotype acyclicity increases_expression of gene/protein APBA3 compared to the 9‚Äď10 month irregular cyclers

Comment	Compared to the 9‚Äď10 month irregular cyclers, the acyclic animals exhibited higher expression of genes involved in fatty acid uptake by the mitochondria (carnitine palmitoyltransferase 2 (Cpt2) and phospholipase A2 group 2A (Pla2g2a)), mitochondrial biogenesis and ATP generation (Atpaf2 and estrogen-related receptor beta (Esrrb)), inflammation (C-X-C motif chemokine 12 (Cxcl12), Cd40, TNF-alpha-induced protein 2 (Tnfaip2)), cholesterol homeostasis (Apoa1 and steroidogenic acute regulatory (Star)), and amyloid and apoptosis related (Apba3 and Bcl2l1).
Formal Description Interaction-ID: 132660	phenotype acyclicity increases_expression of gene/protein BCL2L1 compared to the 9‚Äď10 month irregular cyclers
Drugbank entries	Show/Hide entries for BCL2L1
Drugbank DB07108	4'-FLUORO-1,1'-BIPHENYL-4-CARBOXYLIC ACI ... not specified BCL2L1

Comment	Functional group analyses revealed a decline in irregular cyclers relative to regular cyclers in genes involved in glucose transport, glycolysis, mitochondrial energy-transducing systems (TCA cycle, electron transfer chain, oxidative phosphorylation, mitochondrial biogenesis and dynamics), cellular redox homeostasis, inflammation (adhesion, chemokines, interleukins, phospholipases), Abeta clearance and degradation, apoptosis, and synaptic plasticity.
Formal Description Interaction-ID: 132661	phenotype irregular cycling decreases_expression of gene/protein genes involved in glycolysis compared to regular cyclers

Comment	Functional group analyses revealed a decline in irregular cyclers relative to regular cyclers in genes involved in glucose transport, glycolysis, mitochondrial energy-transducing systems (TCA cycle, electron transfer chain, oxidative phosphorylation, mitochondrial biogenesis and dynamics), cellular redox homeostasis, inflammation (adhesion, chemokines, interleukins, phospholipases), Abeta clearance and degradation, apoptosis, and synaptic plasticity.
Formal Description Interaction-ID: 132662	phenotype irregular cycling decreases_expression of gene/protein genes involved in mitochondrial function compared to regular cyclers, TCA cycle, concerning electron transfer chain, oxidative phosphorylation, mitochondrial biogenesis and dynamics

Comment	Functional group analyses revealed a decline in irregular cyclers relative to regular cyclers in genes involved in glucose transport, glycolysis, mitochondrial energy-transducing systems (TCA cycle, electron transfer chain, oxidative phosphorylation, mitochondrial biogenesis and dynamics), cellular redox homeostasis, inflammation (adhesion, chemokines, interleukins, phospholipases), Abeta clearance and degradation, apoptosis, and synaptic plasticity.
Formal Description Interaction-ID: 132663	phenotype irregular cycling decreases_expression of gene/protein genes involved in cellular redox homeostasis compared to regular cyclers

Comment	Functional group analyses revealed a decline in irregular cyclers relative to regular cyclers in genes involved in glucose transport, glycolysis, mitochondrial energy-transducing systems (TCA cycle, electron transfer chain, oxidative phosphorylation, mitochondrial biogenesis and dynamics), cellular redox homeostasis, inflammation (adhesion, chemokines, interleukins, phospholipases), Abeta clearance and degradation, apoptosis, and synaptic plasticity.
Formal Description Interaction-ID: 132664	phenotype irregular cycling decreases_expression of gene/protein genes involved in inflammation compared to regular cyclers, concerning adhesion, chemokines, interleukins, phospholipases

Comment	Functional group analyses revealed a decline in irregular cyclers relative to regular cyclers in genes involved in glucose transport, glycolysis, mitochondrial energy-transducing systems (TCA cycle, electron transfer chain, oxidative phosphorylation, mitochondrial biogenesis and dynamics), cellular redox homeostasis, inflammation (adhesion, chemokines, interleukins, phospholipases), Abeta clearance and degradation, apoptosis, and synaptic plasticity.
Formal Description Interaction-ID: 132665	phenotype irregular cycling decreases_expression of gene/protein genes involved in Abeta clearance and degradation compared to regular cyclers

Comment	Functional group analyses revealed a decline in irregular cyclers relative to regular cyclers in genes involved in glucose transport, glycolysis, mitochondrial energy-transducing systems (TCA cycle, electron transfer chain, oxidative phosphorylation, mitochondrial biogenesis and dynamics), cellular redox homeostasis, inflammation (adhesion, chemokines, interleukins, phospholipases), Abeta clearance and degradation, apoptosis, and synaptic plasticity.
Formal Description Interaction-ID: 132666	phenotype irregular cycling decreases_expression of gene/protein genes involved in apoptosis compared to regular cyclers

Comment	Functional group analyses revealed a decline in irregular cyclers relative to regular cyclers in genes involved in glucose transport, glycolysis, mitochondrial energy-transducing systems (TCA cycle, electron transfer chain, oxidative phosphorylation, mitochondrial biogenesis and dynamics), cellular redox homeostasis, inflammation (adhesion, chemokines, interleukins, phospholipases), Abeta clearance and degradation, apoptosis, and synaptic plasticity.
Formal Description Interaction-ID: 132667	phenotype irregular cycling decreases_expression of gene/protein genes involved in synaptic plasticity compared to regular cyclers

Comment	Functional group analyses between the 9‚Äď10 month irregular cyclers and acyclic animals revealed that the deficits in glycolytic genes persisted into the acyclic condition. In contrast, mitochondrial genes were increased with the transition into acyclicity and those involved in synaptic plasticity were partially recovered.
Formal Description Interaction-ID: 132668	phenotype acyclicity increases_expression of gene/protein genes involved in mitochondrial function compared 9‚Äď10 month irregular cyclers, deficits in mitochondrial genes were increased with the transition into the acyclic condition

Comment	Functional group analyses between the 9‚Äď10 month irregular cyclers and acyclic animals revealed that the deficits in glycolytic genes persisted into the acyclic condition. In contrast, mitochondrial genes were increased with the transition into acyclicity and those involved in synaptic plasticity were partially recovered.
Formal Description Interaction-ID: 132669	phenotype acyclicity increases_expression of gene/protein genes involved in synaptic plasticity compared 9‚Äď10 month irregular cyclers, genes involved in synaptic plasticity were partially recovered

Comment	In Reg-9‚Äď10m vs Reg-6m the phospholipase PLD1 is upregulated.
Formal Description Interaction-ID: 133264	process menopause transition increases_expression of gene/protein PLD1
Drugbank entries	Show/Hide entries for PLD1
Drugbank DB00122	Choline product of PLD1
Drugbank DB00122	Choline product of PLD1

Comment	In Reg-9‚Äď10m vs Reg-6m HRH1 is upregulated.
Formal Description Interaction-ID: 133272	process menopause transition increases_expression of gene/protein HRH1
Drugbank entries	Show/Hide entries for HRH1
Drugbank DB00245	Benztropine antagonist HRH1
Drugbank DB00246	Ziprasidone antagonist HRH1
Drugbank DB00283	Clemastine antagonist HRH1
Drugbank DB00321	Amitriptyline antagonist HRH1
Drugbank DB00334	Olanzapine antagonist HRH1
Drugbank DB00341	Cetirizine antagonist HRH1
Drugbank DB00342	Terfenadine antagonist HRH1
Drugbank DB00354	Buclizine antagonist HRH1
Drugbank DB00363	Clozapine antagonist HRH1
Drugbank DB00366	Doxylamine antagonist HRH1
Drugbank DB00370	Mirtazapine antagonist HRH1
Drugbank DB00405	Dexbrompheniramine antagonist HRH1
Drugbank DB00420	Promazine antagonist HRH1
Drugbank DB00427	Triprolidine antagonist HRH1
Drugbank DB00434	Cyproheptadine antagonist HRH1
Drugbank DB00455	Loratadine antagonist HRH1
Drugbank DB00458	Imipramine antagonist HRH1
Drugbank DB00540	Nortriptyline antagonist HRH1
Drugbank DB00557	Hydroxyzine antagonist HRH1
Drugbank DB00568	Cinnarizine antagonist HRH1
Drugbank DB00637	Astemizole antagonist HRH1
Drugbank DB00656	Trazodone antagonist HRH1
Drugbank DB00667	Histamine Phosphate agonist HRH1
Drugbank DB00719	Azatadine antagonist HRH1
Drugbank DB00726	Trimipramine antagonist HRH1
Drugbank DB00734	Risperidone antagonist HRH1
Drugbank DB00737	Meclizine antagonist HRH1
Drugbank DB00748	Carbinoxamine antagonist HRH1
Drugbank DB00751	Epinastine antagonist HRH1
Drugbank DB00767	Benzquinamide antagonist HRH1
Drugbank DB00768	Olopatadine antagonist HRH1
Drugbank DB00777	Propiomazine antagonist HRH1
Drugbank DB00792	Tripelennamine antagonist HRH1
Drugbank DB00797	Tolazoline agonist HRH1
Drugbank DB00835	Brompheniramine antagonist HRH1
Drugbank DB00885	Pemirolast antagonist HRH1
Drugbank DB00902	Methdilazine antagonist HRH1
Drugbank DB00920	Ketotifen antagonist HRH1
Drugbank DB00934	Maprotiline antagonist HRH1
Drugbank DB00950	Fexofenadine antagonist HRH1
Drugbank DB00967	Desloratadine antagonist HRH1
Drugbank DB00972	Azelastine antagonist HRH1
Drugbank DB00985	Dimenhydrinate antagonist HRH1
Drugbank DB01069	Promethazine antagonist HRH1
Drugbank DB01071	Mequitazine antagonist HRH1
Drugbank DB01075	Diphenhydramine antagonist HRH1
Drugbank DB01084	Emedastine antagonist HRH1
Drugbank DB01106	Levocabastine antagonist HRH1
Drugbank DB01114	Chlorpheniramine antagonist HRH1
Drugbank DB01142	Doxepin antagonist HRH1
Drugbank DB01146	Diphenylpyraline antagonist HRH1
Drugbank DB01151	Desipramine antagonist HRH1
Drugbank DB01173	Orphenadrine antagonist HRH1
Drugbank DB01175	Escitalopram antagonist HRH1
Drugbank DB01176	Cyclizine antagonist HRH1
Drugbank DB01224	Quetiapine antagonist HRH1
Drugbank DB01237	Bromodiphenhydramine antagonist HRH1
Drugbank DB01238	Aripiprazole antagonist HRH1
Drugbank DB01239	Chlorprothixene antagonist HRH1
Drugbank DB01246	Trimeprazine antagonist HRH1
Drugbank DB01267	Paliperidone agonist HRH1
Drugbank DB01403	Methotrimeprazine antagonist HRH1
Drugbank DB01615	Aceprometazine antagonist HRH1
Drugbank DB01619	Phenindamine antagonist HRH1
Drugbank DB01620	Pheniramine antagonist HRH1
Drugbank DB04837	Chlophedianol antagonist HRH1
Drugbank DB04841	Flunarizine antagonist HRH1
Drugbank DB04890	Bepotastine antagonist HRH1
Drugbank DB06148	Mianserin antagonist HRH1
Drugbank DB06691	Mepyramine antagonist HRH1
Drugbank DB06698	Betahistine agonist HRH1
Drugbank DB06766	Alcaftadine antagonist HRH1
Drugbank DB08799	Antazoline antagonist HRH1
Drugbank DB08800	Chloropyramine antagonist HRH1
Drugbank DB08801	Dimethindene antagonist HRH1
Drugbank DB08802	Isothipendyl antagonist HRH1
Drugbank DB00283	Clemastine antagonist HRH1
Drugbank DB00341	Cetirizine antagonist HRH1
Drugbank DB00342	Terfenadine antagonist HRH1
Drugbank DB00354	Buclizine antagonist HRH1
Drugbank DB00366	Doxylamine antagonist HRH1
Drugbank DB00370	Mirtazapine antagonist HRH1
Drugbank DB00405	Dexbrompheniramine antagonist HRH1
Drugbank DB00427	Triprolidine antagonist HRH1
Drugbank DB00455	Loratadine antagonist HRH1
Drugbank DB00557	Hydroxyzine antagonist HRH1
Drugbank DB00719	Azatadine antagonist HRH1
Drugbank DB00737	Meclizine antagonist HRH1
Drugbank DB00748	Carbinoxamine antagonist HRH1
Drugbank DB00792	Tripelennamine antagonist HRH1
Drugbank DB00835	Brompheniramine antagonist HRH1
Drugbank DB00885	Pemirolast antagonist HRH1
Drugbank DB00902	Methdilazine antagonist HRH1
Drugbank DB00950	Fexofenadine antagonist HRH1
Drugbank DB00967	Desloratadine antagonist HRH1
Drugbank DB00972	Azelastine antagonist HRH1
Drugbank DB00985	Dimenhydrinate antagonist HRH1
Drugbank DB01071	Mequitazine antagonist HRH1
Drugbank DB01075	Diphenhydramine antagonist HRH1
Drugbank DB01084	Emedastine antagonist HRH1
Drugbank DB01106	Levocabastine antagonist HRH1
Drugbank DB01114	Chlorpheniramine antagonist HRH1
Drugbank DB01146	Diphenylpyraline antagonist HRH1
Drugbank DB01237	Bromodiphenhydramine antagonist HRH1
Drugbank DB01246	Trimeprazine antagonist HRH1
Drugbank DB01615	Aceprometazine antagonist HRH1
Drugbank DB01619	Phenindamine antagonist HRH1
Drugbank DB01620	Pheniramine antagonist HRH1
Drugbank DB04837	Chlophedianol antagonist HRH1
Drugbank DB04890	Bepotastine antagonist HRH1

Comment	Compared to the 9‚Äď10 month acyclic group, the 16 month acyclic group exhibited lower expression of gene BCL2L1 involved in apoptosis.
Formal Description Interaction-ID: 133611	phenotype acyclicity decreases_expression of gene/protein BCL2L1 in the 16 month acyclic group; compared to the 9‚Äď10 month acyclic group
Drugbank entries	Show/Hide entries for BCL2L1
Drugbank DB07108	4'-FLUORO-1,1'-BIPHENYL-4-CARBOXYLIC ACI ... not specified BCL2L1

Comment	Compared to the 9‚Äď10 month acyclic group, the 16 month acyclic group exhibited lower expression of gene BCL2L1 involved in apoptosis.
Formal Description Interaction-ID: 133612	gene/protein BCL2L1 affects_activity of process apoptotic process in the 16 month acyclic group; compared to the 9‚Äď10 month acyclic group
Drugbank entries	Show/Hide entries for BCL2L1
Drugbank DB07108	4'-FLUORO-1,1'-BIPHENYL-4-CARBOXYLIC ACI ... not specified BCL2L1

Comment	Compared to the 9‚Äď10 month acyclic group, the 16 month acyclic group exhibited lower expression of gene PPARG involved in lipid metabolism.
Formal Description Interaction-ID: 133926	process menopause transition decreases_expression of gene/protein PPARG in the 16 month acyclic group; compared to the 9‚Äď10 month acyclic group
Drugbank entries	Show/Hide entries for PPARG
Drugbank DB00159	Icosapent agonist PPARG
Drugbank DB00197	Troglitazone agonist PPARG
Drugbank DB00244	Mesalazine agonist PPARG
Drugbank DB00328	Indomethacin activator PPARG
Drugbank DB00412	Rosiglitazone agonist PPARG
Drugbank DB00731	Nateglinide inhibitor PPARG
Drugbank DB00795	Sulfasalazine agonist PPARG
Drugbank DB00912	Repaglinide agonist PPARG
Drugbank DB00966	Telmisartan partial agonist PPARG
Drugbank DB01014	Balsalazide agonist PPARG
Drugbank DB01067	Glipizide agonist PPARG
Drugbank DB01132	Pioglitazone agonist PPARG
Drugbank DB01252	Mitiglinide agonist PPARG
Drugbank DB01393	Bezafibrate agonist PPARG
Drugbank DB04270	(S)-3-(4-(2-Carbazol-9-Yl-Ethoxy)-Phenyl ... not specified PPARG
Drugbank DB04689	2-{5-[3-(6-BENZOYL-1-PROPYLNAPHTHALEN-2- ... not specified PPARG
Drugbank DB06908	(2S)-3-(1-{[2-(2-CHLOROPHENYL)-5-METHYL- ... not specified PPARG
Drugbank DB06926	(9Z,11E,13S)-13-hydroxyoctadeca-9,11-die ... not specified PPARG
Drugbank DB07053	2-{5-[3-(7-PROPYL-3-TRIFLUOROMETHYLBENZO ... not specified PPARG
Drugbank DB07111	(4S,5E,7Z,10Z,13Z,16Z,19Z)-4-hydroxydoco ... not specified PPARG
Drugbank DB07172	(5R,6E,8Z,11Z,14Z,17Z)-5-hydroxyicosa-6, ... not specified PPARG
Drugbank DB07208	(8E,10S,12Z)-10-hydroxy-6-oxooctadeca-8, ... not specified PPARG
Drugbank DB07209	(8R,9Z,12Z)-8-hydroxy-6-oxooctadeca-9,12 ... not specified PPARG
Drugbank DB07302	(9S,10E,12Z)-9-hydroxyoctadeca-10,12-die ... not specified PPARG
Drugbank DB07509	difluoro(5-{2-[(5-octyl-1H-pyrrol-2-yl-k ... not specified PPARG
Drugbank DB07675	(2S)-2-ETHOXY-3-{4-[2-(10H-PHENOXAZIN-10 ... not specified PPARG
Drugbank DB07723	3-(5-methoxy-1H-indol-3-yl)propanoic aci ... not specified PPARG
Drugbank DB07724	3-{5-methoxy-1-[(4-methoxyphenyl)sulfony ... not specified PPARG
Drugbank DB07842	(2S)-2-(4-ethylphenoxy)-3-phenylpropanoi ... not specified PPARG
Drugbank DB07863	2-chloro-5-nitro-N-phenylbenzamide not specified PPARG
Drugbank DB08121	(2S)-2-(biphenyl-4-yloxy)-3-phenylpropan ... not specified PPARG
Drugbank DB08302	3-[5-(2-nitropent-1-en-1-yl)furan-2-yl]b ... not specified PPARG
Drugbank DB08402	2-[(2,4-DICHLOROBENZOYL)AMINO]-5-(PYRIMI ... not specified PPARG
Drugbank DB08435	(5E,14E)-11-oxoprosta-5,9,12,14-tetraen- ... not specified PPARG
Drugbank DB08483	(2S)-2-methoxy-3-{4-[2-(5-methyl-2-pheny ... not specified PPARG
Drugbank DB08560	3-FLUORO-N-[1-(4-FLUOROPHENYL)-3-(2-THIE ... not specified PPARG
Drugbank DB08760	(2S)-2-(4-chlorophenoxy)-3-phenylpropano ... not specified PPARG
Drugbank DB00197	Troglitazone agonist PPARG
Drugbank DB00412	Rosiglitazone agonist PPARG
Drugbank DB01132	Pioglitazone agonist PPARG
Drugbank DB04689	2-{5-[3-(6-BENZOYL-1-PROPYLNAPHTHALEN-2- ... not specified PPARG

Comment	Compared to the 9‚Äď10 month acyclic group, the 16 month acyclic group exhibited lower expression of gene PPARG involved in lipid metabolism.
Formal Description Interaction-ID: 133927	gene/protein PPARG affects_activity of process lipid metabolic process in the 16 month acyclic group; compared to the 9‚Äď10 month acyclic group
Drugbank entries	Show/Hide entries for PPARG
Drugbank DB00159	Icosapent agonist PPARG
Drugbank DB00197	Troglitazone agonist PPARG
Drugbank DB00244	Mesalazine agonist PPARG
Drugbank DB00328	Indomethacin activator PPARG
Drugbank DB00412	Rosiglitazone agonist PPARG
Drugbank DB00731	Nateglinide inhibitor PPARG
Drugbank DB00795	Sulfasalazine agonist PPARG
Drugbank DB00912	Repaglinide agonist PPARG
Drugbank DB00966	Telmisartan partial agonist PPARG
Drugbank DB01014	Balsalazide agonist PPARG
Drugbank DB01067	Glipizide agonist PPARG
Drugbank DB01132	Pioglitazone agonist PPARG
Drugbank DB01252	Mitiglinide agonist PPARG
Drugbank DB01393	Bezafibrate agonist PPARG
Drugbank DB04270	(S)-3-(4-(2-Carbazol-9-Yl-Ethoxy)-Phenyl ... not specified PPARG
Drugbank DB04689	2-{5-[3-(6-BENZOYL-1-PROPYLNAPHTHALEN-2- ... not specified PPARG
Drugbank DB06908	(2S)-3-(1-{[2-(2-CHLOROPHENYL)-5-METHYL- ... not specified PPARG
Drugbank DB06926	(9Z,11E,13S)-13-hydroxyoctadeca-9,11-die ... not specified PPARG
Drugbank DB07053	2-{5-[3-(7-PROPYL-3-TRIFLUOROMETHYLBENZO ... not specified PPARG
Drugbank DB07111	(4S,5E,7Z,10Z,13Z,16Z,19Z)-4-hydroxydoco ... not specified PPARG
Drugbank DB07172	(5R,6E,8Z,11Z,14Z,17Z)-5-hydroxyicosa-6, ... not specified PPARG
Drugbank DB07208	(8E,10S,12Z)-10-hydroxy-6-oxooctadeca-8, ... not specified PPARG
Drugbank DB07209	(8R,9Z,12Z)-8-hydroxy-6-oxooctadeca-9,12 ... not specified PPARG
Drugbank DB07302	(9S,10E,12Z)-9-hydroxyoctadeca-10,12-die ... not specified PPARG
Drugbank DB07509	difluoro(5-{2-[(5-octyl-1H-pyrrol-2-yl-k ... not specified PPARG
Drugbank DB07675	(2S)-2-ETHOXY-3-{4-[2-(10H-PHENOXAZIN-10 ... not specified PPARG
Drugbank DB07723	3-(5-methoxy-1H-indol-3-yl)propanoic aci ... not specified PPARG
Drugbank DB07724	3-{5-methoxy-1-[(4-methoxyphenyl)sulfony ... not specified PPARG
Drugbank DB07842	(2S)-2-(4-ethylphenoxy)-3-phenylpropanoi ... not specified PPARG
Drugbank DB07863	2-chloro-5-nitro-N-phenylbenzamide not specified PPARG
Drugbank DB08121	(2S)-2-(biphenyl-4-yloxy)-3-phenylpropan ... not specified PPARG
Drugbank DB08302	3-[5-(2-nitropent-1-en-1-yl)furan-2-yl]b ... not specified PPARG
Drugbank DB08402	2-[(2,4-DICHLOROBENZOYL)AMINO]-5-(PYRIMI ... not specified PPARG
Drugbank DB08435	(5E,14E)-11-oxoprosta-5,9,12,14-tetraen- ... not specified PPARG
Drugbank DB08483	(2S)-2-methoxy-3-{4-[2-(5-methyl-2-pheny ... not specified PPARG
Drugbank DB08560	3-FLUORO-N-[1-(4-FLUOROPHENYL)-3-(2-THIE ... not specified PPARG
Drugbank DB08760	(2S)-2-(4-chlorophenoxy)-3-phenylpropano ... not specified PPARG
Drugbank DB00197	Troglitazone agonist PPARG
Drugbank DB00412	Rosiglitazone agonist PPARG
Drugbank DB01132	Pioglitazone agonist PPARG
Drugbank DB04689	2-{5-[3-(6-BENZOYL-1-PROPYLNAPHTHALEN-2- ... not specified PPARG

Comment	Compared to the 9‚Äď10 month acyclic group, the 16 month acyclic group exhibited lower expression of gene PPARG involved in lipid metabolism.
Formal Description Interaction-ID: 133985	gene/protein PLA2G1B affects_activity of process lipid metabolic process in the 16 month acyclic group; compared to the 9‚Äď10 month acyclic group
Drugbank entries	Show/Hide entries for PLA2G1B
Drugbank DB02210	Hexane-1,6-Diol not specified PLA2G1B
Drugbank DB02448	N-Tridecanoic Acid not specified PLA2G1B
Drugbank DB02659	Cholic Acid not specified PLA2G1B
Drugbank DB02795	P-Anisic Acid not specified PLA2G1B
Drugbank DB02938	Heptanoic Acid not specified PLA2G1B
Drugbank DB02944	Alpha-D-Mannose not specified PLA2G1B
Drugbank DB03565	1-O-Octyl-2-Heptylphosphonyl-Sn-Glycero- ... not specified PLA2G1B
Drugbank DB03587	Pyruvoyl Group not specified PLA2G1B
Drugbank DB03633	Lpc-Ether not specified PLA2G1B
Drugbank DB04552	Niflumic Acid inhibitor PLA2G1B
Drugbank DB07657	PHOSPHONIC ACID 2-DODECANOYLAMINO-HEXYL ... not specified PLA2G1B
Drugbank DB07836	1-DECYL-3-TRIFLUORO ETHYL-SN-GLYCERO-2-P ... not specified PLA2G1B
Drugbank DB02210	Hexane-1,6-Diol not specified PLA2G1B
Drugbank DB02795	P-Anisic Acid not specified PLA2G1B
Drugbank DB02938	Heptanoic Acid not specified PLA2G1B
Drugbank DB02944	Alpha-D-Mannose not specified PLA2G1B
Drugbank DB03565	1-O-Octyl-2-Heptylphosphonyl-Sn-Glycero- ... not specified PLA2G1B
Drugbank DB03587	Pyruvoyl Group not specified PLA2G1B
Drugbank DB03633	Lpc-Ether not specified PLA2G1B

Comment	Compared to the 9‚Äď10 month acyclic group, the 16 month acyclic group exhibited lower expression of gene PPARG involved in lipid metabolism.
Formal Description Interaction-ID: 133986	process menopause transition decreases_expression of gene/protein PLA2G1B in the 16 month acyclic group; compared to the 9‚Äď10 month acyclic group
Drugbank entries	Show/Hide entries for PLA2G1B
Drugbank DB02210	Hexane-1,6-Diol not specified PLA2G1B
Drugbank DB02448	N-Tridecanoic Acid not specified PLA2G1B
Drugbank DB02659	Cholic Acid not specified PLA2G1B
Drugbank DB02795	P-Anisic Acid not specified PLA2G1B
Drugbank DB02938	Heptanoic Acid not specified PLA2G1B
Drugbank DB02944	Alpha-D-Mannose not specified PLA2G1B
Drugbank DB03565	1-O-Octyl-2-Heptylphosphonyl-Sn-Glycero- ... not specified PLA2G1B
Drugbank DB03587	Pyruvoyl Group not specified PLA2G1B
Drugbank DB03633	Lpc-Ether not specified PLA2G1B
Drugbank DB04552	Niflumic Acid inhibitor PLA2G1B
Drugbank DB07657	PHOSPHONIC ACID 2-DODECANOYLAMINO-HEXYL ... not specified PLA2G1B
Drugbank DB07836	1-DECYL-3-TRIFLUORO ETHYL-SN-GLYCERO-2-P ... not specified PLA2G1B
Drugbank DB02210	Hexane-1,6-Diol not specified PLA2G1B
Drugbank DB02795	P-Anisic Acid not specified PLA2G1B
Drugbank DB02938	Heptanoic Acid not specified PLA2G1B
Drugbank DB02944	Alpha-D-Mannose not specified PLA2G1B
Drugbank DB03565	1-O-Octyl-2-Heptylphosphonyl-Sn-Glycero- ... not specified PLA2G1B
Drugbank DB03587	Pyruvoyl Group not specified PLA2G1B
Drugbank DB03633	Lpc-Ether not specified PLA2G1B

Comment	The insulin/IGF1 signaling cascade from IRS1, to Akt and ERK1/2 were substantially decreased in the irregular cyclers; this pattern was accompanied by the decline in transcriptional pathways CREB.
Formal Description Interaction-ID: 134762	process aging decreases_activity of process Insulin/IGF1 signaling pathway in the irregular cyclers

Comment	The insulin/IGF1 signaling cascade from IRS1, to Akt and ERK1/2 were substantially decreased in the irregular cyclers; this pattern was accompanied by the decline in transcriptional pathways CREB.
Formal Description Interaction-ID: 134763	phenotype irregular cycling decreases_activity of process Insulin/IGF1 signaling pathway in the irregular cyclers

Comment	Impaired insulin/IGF1 signaling during brain aging was shown in AD animal models and patients.
Formal Description Interaction-ID: 134764	process aging increases_activity of phenotype impaired insulin/IGF1 signaling pathway in AD animal models and patients

Comment	The insulin/IGF1 signaling cascade from IRS1, to Akt and ERK1/2 were substantially decreased in the irregular cyclers; this pattern was accompanied by the decline in transcriptional pathways CREB and AMPK. The levels of phosphorylated (activated) ERK1 and ERK2 were decreased in irregular cycling rats compared to regular cycling rats.
Formal Description Interaction-ID: 135324	phenotype irregular cycling decreases_quantity of protein modification MAPK3-phos compared to regular cycling rats

Comment	The insulin/IGF1 signaling cascade from IRS1, to Akt and ERK1/2 were substantially decreased in the irregular cyclers; this pattern was accompanied by the decline in transcriptional pathways CREB and AMPK. The levels of phosphorylated (activated) ERK1 and ERK2 were decreased in irregular cycling rats compared to regular cycling rats.
Formal Description Interaction-ID: 135325	phenotype irregular cycling decreases_quantity of protein modification MAPK1-phos compared to regular cycling rats

Comment	The insulin/IGF1 signaling cascade from IRS1, to Akt and ERK1/2 were substantially decreased in the irregular cyclers; this pattern was accompanied by the decline in transcriptional pathways CREB and AMPK. The levels of phosphorylated (activated) ERK1 and ERK2 were decreased in irregular cycling rats compared to regular cycling rats.
Formal Description Interaction-ID: 135326	process aging decreases_quantity of protein modification MAPK3-phos irregular cycling rats compared to regular cycling rats

Comment	The insulin/IGF1 signaling cascade from IRS1, to Akt and ERK1/2 were substantially decreased in the irregular cyclers; this pattern was accompanied by the decline in transcriptional pathways CREB and AMPK. The levels of phosphorylated (activated) ERK1 and ERK2 were decreased in irregular cycling rats compared to regular cycling rats.
Formal Description Interaction-ID: 135327	process aging decreases_quantity of protein modification MAPK1-phos irregular cycling rats compared to regular cycling rats