Neuroactive steroids modulate GABA inhibition of hypothalamic somatostatin release

Abstract
The reduced steroids 3α-hydroxy-5α-pregnan-20-one (allopregnanolone) and 3α,21-di-hydroxy-5α-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 3α-hydroxysteroids modulate GABA inhibition of hypothalamic somatostatin release.

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