Progesterone-metabolite prevents protein kinase c-dependent modulation of γ-aminobutyric acid type A receptors in oxytocin neurons

Arjen B. Brussaard, Juriaan Wossink, Johannes C. Lodder, Karel S. Kits

Research output: Contribution to journalArticleAcademicpeer-review


Gonadal steroid feedback to oxytocin neurons during pregnancy is in part mediated via the neurosteroid allopregnanolone (3α-OH-DHP), acting as allosteric modulator of postsynaptic γ-aminobutyric acid type A (GABA(A)) receptors. We describe here a form of nongenomic progesterone signaling by showing that 3α-OH-DHP not only potentiates GABA(A) receptor-channel activity but also prevents its modulation by protein kinase C (PKC). Application of oxytocin or stimulation of PKC suppressed the postsynaptic GABA responses of oxytocin neurons in the absence, but not in the presence of 3α-OH-DHP. This finding was true at the juvenile stage and during late pregnancy, when the GABA(A) receptor is sensitive to 3α-OH-DHP. In contrast, after parturition, when the GABA(A) receptors expressed by oxytocin neurons are less sensitive to 3α-OH-DHP, this neurosteroid no longer counteracts PKC. The change in GABA(A)-receptor responsiveness to 3α-OH-DHP helps to explain the onset of firing activity and thus the induction of oxytocin release at parturition.
Original languageEnglish
Pages (from-to)3625-3630
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number7
Publication statusPublished - 28 Mar 2000
Externally publishedYes

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