Document Detail


gamma-Aminobutyric acid, acting through gamma -aminobutyric acid type A receptors, inhibits the biosynthesis of neurosteroids in the frog hypothalamus.
MedLine Citation:
PMID:  11087816     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Most of the actions of neurosteroids on the central nervous system are mediated through allosteric modulation of the gamma-aminobutyric acid type A (GABA(A)) receptor, but a direct effect of GABA on the regulation of neurosteroid biosynthesis has never been investigated. In the present report, we have attempted to determine whether 3beta-hydroxysteroid dehydrogenase (3beta-HSD)-containing neurons, which secrete neurosteroids in the frog hypothalamus, also express the GABA(A) receptor, and we have investigated the effect of GABA on neurosteroid biosynthesis by frog hypothalamic explants. Double immunohistochemical labeling revealed that most 3beta-HSD-positive neurons also contain GABA(A) receptor alpha(3) and beta(2)/beta(3) subunit-like immunoreactivities. Pulse-chase experiments showed that GABA inhibited in a dose-dependent manner the conversion of tritiated pregnenolone into radioactive steroids, including 17-hydroxy-pregnenolone, progesterone, 17-hydroxy-progesterone, dehydroepiandrosterone, and dihydrotestosterone. The effect of GABA on neurosteroid biosynthesis was mimicked by the GABA(A) receptor agonist muscimol but was not affected by the GABA(B) receptor agonist baclofen. The selective GABA(A) receptor antagonists bicuculline and SR95531 reversed the inhibitory effect of GABA on neurosteroid formation. The present results indicate that steroid-producing neurons of the frog hypothalamus express the GABA(A) receptor alpha(3) and beta(2)/beta(3) subunits. Our data also demonstrate that GABA, acting on GABA(A) receptors at the hypothalamic level, inhibits the activity of several key steroidogenic enzymes, including 3beta-HSD and cytochrome P450(C17) (17alpha-hydroxylase).
Authors:
J L Do-Rego; G A Mensah-Nyagan; D Beaujean; D Vaudry; W Sieghart; V Luu-The; G Pelletier; H Vaudry
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  97     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2000-12-18     Completed Date:  2001-01-18     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  13925-30     Citation Subset:  IM    
Affiliation:
European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, Institut National de la Santé et de la Recherche Médicale, Unité 413, Centre National de la Recherche Scientifique, University of Rouen, Franceg
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MeSH Terms
Descriptor/Qualifier:
Animals
Fluorescent Antibody Technique
GABA-A Receptor Agonists
GABA-A Receptor Antagonists
Hypothalamus / physiology*
Immunohistochemistry
Male
Rana ridibunda
Receptors, GABA-A / physiology*
Steroids / antagonists & inhibitors*,  biosynthesis
gamma-Aminobutyric Acid / physiology*
Chemical
Reg. No./Substance:
0/GABA-A Receptor Agonists; 0/GABA-A Receptor Antagonists; 0/Receptors, GABA-A; 0/Steroids; 56-12-2/gamma-Aminobutyric Acid
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