Av. Sirotkin et al., Effect of four cGMP analogues with different mechanisms of action on hormone release by porcine ovarian granulosa cells in vitro, EXP CL E D, 108(3), 2000, pp. 214-219
Citations number
34
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES
The aim of our in-vitro experiments was to examine the role of cGMP-depende
nt intracellular mechanisms in control of ovarian hormone secretion. as wel
l as to understand. whether cGMP effect on the ovary may be mediated by eit
her protein kinase G (PKG), cGMP-gated ion channels (CGI) or cGMP-specific
phosphodiesterases (PDE).
We compared the effects of the cGMP analogues 8-pCPT-cGMP. an activator of
PKG 1-alpha, 1-beta and type II and of CGI, but not of PDE: Rp-8-pCPT-cGMPS
and Rp-8-Br-cGMPS, inhibitors of PKG, stimulators of CGI with no effect of
PDE, and Rp-8-Br-PET-cGMPS, an inhibitor of both. PKG and CGI and stimulat
or of PDE (all at 0.01- 0.1, 1, 10 or 100 nM), on the release of oxytocin (
OT) and progesterone (P) by cultured porcine granulosa cells.
It was observed, that Rp-8-pCPT-cGMPS significantly (p<0.05) suppressed OT
release when given at 1 or 10 nM. Rp-8-Br-cGMPS increased OT output, when g
iven at 1-10 nM too, but decreased it at 100 nM. Rp-8-Br-PET-cGMPS inhibite
d OT release at 1 nM. No influence of 8-pCPT-cGMP on OT output was round, 8
-pCPT-cGMP stimulated P release at 0.1, 10 or 100 nM. All other cGMP analog
ues studied suppressed P release at all doses used.
The present observations suggest the involvement of cGMP-dependent intracel
lular mechanims in control of ovarian steroid and nonapeptide hormone relea
se. The lack of association between patterns of influence of cGMP analogues
on CGI and PDE, and the coincidence of the majority of effects of cGMP ana
logues on P, OT and PKG may indirectly indicate that cGMP action on release
of. ovarian hormones is mediated mainly by PRG, but not by CGI or PDE.