TY - JOUR
T1 - Progesterone-metabolite prevents protein kinase C-dependent modulation of gamma-aminobutyric acid type A receptor in oxytocin neurons
AU - Brussaard, A.B.
AU - Wossink, J.
AU - Lodder, J.C.
AU - Kits, K.S.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
U2 - 10.1073/pnas.050424697
DO - 10.1073/pnas.050424697
M3 - Article
VL - 97
SP - 3625
EP - 3630
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 7
ER -
