Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain

Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically,...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2011-03, Vol.108 (10), p.4242-4247
Hauptverfasser: Auger, Catherine J, Coss, Dylan, Auger, Anthony P, Forbes-Lorman, Robin M
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creator Auger, Catherine J
Coss, Dylan
Auger, Anthony P
Forbes-Lorman, Robin M
description Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the socially relevant peptide vasopressin (AVP) within the bed nucleus of the stria terminalis (BST) of adult brain is dependent upon testosterone exposure. Castration dramatically reduces and testosterone replacement restores AVP expression within the BST. As decreases in mRNA expression are associated with increases in DNA promoter methylation, we explored the hypothesis that AVP expression in the adult brain is maintained through sustained epigenetic modifications of the AVP gene promoter. We find that castration of adult male rats resulted in decreased AVP mRNA expression and increased methylation of specific CpG sites within the AVP promoter in the BST. Similarly, castration significantly increased estrogen receptor α (ERα) mRNA expression and decreased ERα promoter methylation within the BST. These changes were prevented by testosterone replacement. This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. The maintenance of methylated or demethylated states of some genes in the adult brain by the presence of steroid hormones may play a role in the homeostatic regulation of behaviorally relevant systems.
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Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the socially relevant peptide vasopressin (AVP) within the bed nucleus of the stria terminalis (BST) of adult brain is dependent upon testosterone exposure. Castration dramatically reduces and testosterone replacement restores AVP expression within the BST. As decreases in mRNA expression are associated with increases in DNA promoter methylation, we explored the hypothesis that AVP expression in the adult brain is maintained through sustained epigenetic modifications of the AVP gene promoter. We find that castration of adult male rats resulted in decreased AVP mRNA expression and increased methylation of specific CpG sites within the AVP promoter in the BST. Similarly, castration significantly increased estrogen receptor α (ERα) mRNA expression and decreased ERα promoter methylation within the BST. These changes were prevented by testosterone replacement. This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. 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This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. 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subjects Animals
Arginine Vasopressin - genetics
Arginine Vasopressin - metabolism
Argipressin
Base Sequence
bed nucleus
Biological Sciences
Brain
Brain - metabolism
Castration
CpG islands
Deoxyribonucleic acid
DNA
DNA Methylation
Enzymes
Epigenesis, Genetic
Epigenetics
Estrogen Receptor alpha - genetics
Estrogen receptors
Estrogens
Gene expression
Gene expression regulation
Homeostasis
Hormonal regulation
Hormones
Hormones - metabolism
Male
Males
Messenger RNA
Methylation
Molecular Sequence Data
Orchiectomy
Promoter Regions, Genetic
Promoters
Rats
RNA, Messenger - genetics
Rodents
Steroid hormones
Steroids
Steroids - metabolism
Stria terminalis
Testosterone
Vasopressin
title Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain
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