Effect of four cGMP analogues with different mechanisms of action on hormone release by porcine ovarian granulosa cells in vitro.
The aim of our in-vitro experiments was to examine the role of cGMP-dependent intracellular mechanisms in control of ovarian hormone secretion, as well as to understand, whether cGMP effect on the ovary may be mediated by either 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 stimulator 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 given at 1-10 nM too, but decreased it at 100 nM. Rp-8-Br-PET-cGMPS inhibited OT release at 1 nM. No influence of 8-pCPT-cGMP on OT output was found. 8-pCPT-cGMP stimulated P release at 0.1, 10 or 100 nM. All other cGMP analogues studied suppressed P release at all doses used. The present observations suggest the involvement of cGMP-dependent intracellular mechanisms in control of ovarian steroid and nonapeptide hormone release. 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 analogues on P, OT and PKG may indirectly indicate that cGMP action on release of ovarian hormones is mediated mainly by PKG, but not by CGI or PDE.
Sirotkin
A V
AV
Research Institute of Animal Production, Nitra, Slovakia. sirotkin@vuzv.sk
Makarevich
A V
AV
Genieser
H G
HG
Kotwica
J
J
Hetényi
L
L
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D013552:Swine; D013873:Thionucleotides / Q000494:pharmacology*
C090860:8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate; D004791:Enzyme Inhibitors; D013873:Thionucleotides; D011374:Progesterone; D010121:Oxytocin; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D017869:Cyclic GMP-Dependent Protein Kinases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP