title: Pregnancy and lactation differentially modify the transcriptional regulation of steroidogenic enzymes through DNA methylation mechanisms in the hippocampus of aged rats.
abstract: In the present study, we examined the mRNA expression and DNA methylation state of steroidogenic enzymes in the hippocampus of young adult (90-days-old) and middle-aged (450-days-old) nulliparous rats, and middle-aged multiparous rats subjected to three pregnancies with and without lactation. Aging decreased the mRNA levels of steroidogenic-related genes, while pregnancy and lactation significantly reduced the effect of aging, maintaining high expression levels of cytochrome P450 side-chain cleavage (P450scc), steroid 5α-reductase-1 (5αR-1), cytochrome P450arom (P450arom) and aldosterone synthase (P450(11β)-2). In addition, pregnancy and lactation diminished the methylation state of the 5αR-1 promoter and increased the transcription of brain-derived neurotrophic factor, synaptophysin and spinophilin. Pregnancy without lactation increased P450scc and 5αR-1 gene expression and decreased the methylation of their promoters. We concluded that the age-related decrease in the mRNA expression of steroidogenic enzymes is differentially attenuated by pregnancy and lactation in the rat hippocampus and that differential methylation mechanisms could be involved.
authors.affiliation: Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral-CONICET, Santa Fe, Argentina. Electronic address: mfrossetti@fbcb.unl.edu.ar.
authors.forename: María F
authors.initials: MF
authors.lastname: Rossetti
authors.affiliation: Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral-CONICET, Santa Fe, Argentina. Electronic address: varayoud@fbcb.unl.edu.ar.
authors.forename: Jorgelina
authors.initials: J
authors.lastname: Varayoud
authors.affiliation: Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral-CONICET, Santa Fe, Argentina. Electronic address: gplazzarino@hotmail.com.
authors.forename: Gisela P
authors.initials: GP
authors.lastname: Lazzarino
authors.affiliation: Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral-CONICET, Santa Fe, Argentina. Electronic address: eluque@fbcb.unl.edu.ar.
authors.forename: Enrique H
authors.initials: EH
authors.lastname: Luque
authors.affiliation: Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina; Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral-CONICET, Santa Fe, Argentina. Electronic address: gramos@fbcb.unl.edu.ar.
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Ramos
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001141:Aromatase; D053898:Biosynthetic Pathways; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003198:Computer Simulation; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000201:enzymology*; D007774:Lactation / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D013256:Steroids / Q000096:biosynthesis*; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D000099273:Neurabins
chemical_list: D001141:Aromatase; D019208:Brain-Derived Neurotrophic Factor; D002786:Cholesterol Side-Chain Cleavage Enzyme; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D013256:Steroids; D016708:Synaptophysin; D000099273:Neurabins
keywords: Aging; DNA methylation; Hippocampus; Maternal experience; Neurosteroidogenic enzymes