385993

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385993 [2018/11/20 14:26] (current)
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 +====== A progesterone metabolite stimulates the release of gonadotropin-releasing hormone from GT1-1 hypothalamic neurons via the gamma-aminobutyric acid type A receptor.======
 +
 +** Article date:** 1995/4/25
 +~~META:date created = 1995-04-25~~
 +
 +** PubMed ID: 385993 **
 +
 +** Journal name: Proceedings of the National Academy of Sciences of the United States of America (ISSN: 0027-8424) **
 +
 +** ABSTRACT **
 +
 +The reduced progesterone metabolite tetrahydroprogesterone (3 alpha-hydroxy-5 alpha-pregnan-20-one;​ 3 alpha,5 alpha-THP) is a positive modulator of the gamma-aminobutyric acid type A (GABAA) receptor. Experiments performed in vitro with hypothalamic fragments have previously shown that GABA could modulate the release of gonadotropin-releasing hormone (GnRH). Using GT1-1 immortalized GnRH neurons, we investigated the role of GABAA receptor ligands, including 3 alpha,5 alpha-THP, on the release of GnRH. We first characterized the GABAA receptors expressed by these neurons. [3H]Muscimol,​ but not [3H]flunitrazepam,​ bound with high affinity to GT1-1 cell membranes (Kd = 10.9 +/- 0.3 nM; Bmax = 979 +/- 12 fmol/mg of protein), and [3H]muscimol binding was enhanced by 3 alpha,5 alpha-THP. mRNAs encoding the alpha 1 and beta 3 subunits of the GABAA receptor were detected by the reverse transcriptase polymerase chain reaction. In agreement with binding data, the benzodiazepine-binding gamma subunit mRNA was absent. GnRH release studies showed a dose-related stimulating action of muscimol. 3 alpha,5 alpha-THP not only modulated muscimol-induced secretion but also stimulated GnRH release when administered alone. Bicuculline and picrotoxin blocked the effects of 3 alpha,5 alpha-THP and muscimol. Finally, we observed that GT1-1 neurons convert progesterone to 3 alpha,5 alpha-THP. We propose that progesterone may increase the release of GnRH by a membrane mechanism, via its reduced metabolite 3 alpha,5 alpha-THP acting at the GABAA receptor.
 +
 +===== ===== 
 +
 +Author List: el-Etr M, Akwa Y, Fiddes R J, Robel P, Baulieu E E
 +
 +Publication Types: Journal Article
 +
 +Substances mentioned in the article: Anti-Anxiety Agents; RNA, Messenger; Receptors, GABA-A; Muscimol; Gonadotropin-Releasing Hormone; Progesterone;​ Flunitrazepam;​ Pregnanolone; ​
 +
 +Mesh terms: Animals; Anti-Anxiety Agents/​pharmacology;​ Brain/​physiology;​ Cell Line; Dose-Response Relationship,​ Drug; Flunitrazepam/​metabolism;​ Gene Expression; Gonadotropin-Releasing Hormone/​secretion;​ Hypothalamus/​drug effects; Kinetics; Muscimol/​metabolism;​ Neurons/​drug effects; Pregnanolone/​pharmacology;​ Progesterone/​metabolism;​ RNA, Messenger/​biosynthesis;​ Rats; Receptors, GABA-A/​biosynthesis; ​
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 +Citations: ​  - //​[[4572738]]//​
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 +  - //​[[385993]]//​
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 +{{tag> Flunitrazepam Receptors,​_GABA-A RNA,​_Messenger Pregnanolone Gonadotropin-Releasing_Hormone Muscimol Progesterone Anti-Anxiety_Agents }}
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 +{{keywords>​ Flunitrazepam,​ Receptors, GABA-A, RNA, Messenger, Pregnanolone,​ Gonadotropin-Releasing Hormone, Muscimol, Progesterone,​ Anti-Anxiety Agents}}
 +
  
385993.txt ยท Last modified: 2018/11/20 14:26 (external edit)