Progesterone-metabolite prevents protein kinase C-dependent modulation of gamma-aminobutyric acid type A receptor in oxytocin neurons

A.B. Brussaard, J. Wossink, J.C. Lodder, K.S. Kits

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number7
DOIs
Publication statusPublished - 2000

Fingerprint

Dive into the research topics of 'Progesterone-metabolite prevents protein kinase C-dependent modulation of gamma-aminobutyric acid type A receptor in oxytocin neurons'. Together they form a unique fingerprint.

Cite this