Neuroactive steroids modulate GABA inhibition of hypothalamic somatostatin release.
The reduced steroids 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) and 3 alpha,21-di-hydroxy-5 alpha-pregnan-20-one (allotetrahydroDOC) are potent ligands of GABAA receptors. This study examined the possible modulatory effect of these metabolites on GABA inhibition of somatostatin release in cultured hypothalamic neurones. Allopregnanolone potentiates GABA inhibition, and reversed picrotoxin and bicuculline-induced augmentation of somatostatin release in a dose-dependent manner. AllotetrahydroDOC also inhibits the stimulated release induced by the antagonists, but did not modify that induced by depolarizing concentrations of K+. Pregnenolone sulphate had no effect on picrotoxin-induced somatostatin release. These findings clearly establish that 3 alpha-hydroxysteroids modulate GABA inhibition of hypothalamic somatostatin release.
URA 1197 CNRS, Université de Montpellier 2, France.
L
L
Tapia-Arancibia
M
M
André
J
J
Belmar
S
S
Arancibia
D000818:Animals; D001640:Bicuculline / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010852:Picrotoxin / Q000037:antagonists & inhibitors; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000378:metabolism*
D001640:Bicuculline; D003900:Desoxycorticosterone; D018756:GABA Antagonists; D018757:GABA Modulators; D010852:Picrotoxin; D011280:Pregnanolone; D013004:Somatostatin; C009413:tetrahydrodeoxycorticosterone