Document Detail

Histone deacetylation during brain development is essential for permanent masculinization of sexual behavior.
MedLine Citation:
PMID:  21586557     Owner:  NLM     Status:  MEDLINE    
Epigenetic histone modifications are emerging as important mechanisms for conveyance of and maintenance of effects of the hormonal milieu to the developing brain. We hypothesized that alteration of histone acetylation status early in development by sex steroid hormones is important for sexual differentiation of the brain. It was found that during the critical period for sexual differentiation, histones associated with promoters of essential genes in masculinization of the brain (estrogen receptor α and aromatase) in the medial preoptic area, an area necessary for male sexual behavior, were differentially acetylated between the sexes. Consistent with these findings, binding of histone deacetylase (HDAC) 2 and 4 to the promoters was higher in males than in females. To examine the involvement of histone deacetylation on masculinization of the brain at the behavioral level, we inhibited HDAC in vivo by intracerebroventricular infusion of the HDAC inhibitor trichostatin A or antisense oligodeoxynucleotide directed against the mRNA for HDAC2 and -4 in newborn male rats. Aspects of male sexual behavior in adulthood were significantly reduced by administration of either trichostatin A or antisense oligodeoxynucleotide. These results demonstrate that HDAC activity during the early postnatal period plays a crucial role in the masculinization of the brain via modifications of histone acetylation status.
Ken Ichi Matsuda; Hiroko Mori; Bridget M Nugent; Donald W Pfaff; Margaret M McCarthy; Mitsuhiro Kawata
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-17
Journal Detail:
Title:  Endocrinology     Volume:  152     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-23     Completed Date:  2011-09-02     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2760-7     Citation Subset:  AIM; IM    
Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
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MeSH Terms
Animals, Newborn
Aromatase / genetics,  metabolism
Brain / growth & development*,  metabolism*
DNA-Binding Proteins / metabolism
Estrogen Receptor alpha / genetics,  metabolism
Histone Deacetylase 2 / antagonists & inhibitors,  metabolism*
Histone Deacetylase Inhibitors / administration & dosage,  pharmacology
Histone Deacetylases / chemistry,  metabolism*
Histones / metabolism*
Infusions, Intraventricular
Oligodeoxyribonucleotides, Antisense / administration & dosage,  pharmacology
Preoptic Area / growth & development,  metabolism
Promoter Regions, Genetic
Rats, Sprague-Dawley
Sex Characteristics
Sex Differentiation*
Sexual Behavior, Animal* / drug effects
Grant Support
R01MH52716-010/MH/NIMH NIH HHS
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Estrogen Receptor alpha; 0/Histone Deacetylase Inhibitors; 0/Histones; 0/Oligodeoxyribonucleotides, Antisense; EC; EC protein, rat; EC protein, rat; EC Deacetylase 2; EC Deacetylases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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