title: Effects of protein kinase A and C inhibitors on follicular inhibin and activin during ovulation.
abstract: Ovulation is associated with a rise in activin A and a decline in pro-alpha C, inhibin A and inhibin B secretion. It is believed that the actions of inhibin and activin during human chorionic gonadotrophin (HCG) stimulation are mediated by protein kinase A (PKA) and/or protein kinase C (PKC). Using an in-vitro murine prenatal follicle culture model, the effects of a PKA inhibitor, Rp-cAMP, and a PKC inhibitor, PKIM, on inhibin and activin gene expression, secretion, ovulation and oocyte maturation were studied during HCG stimulation. Both Rp-cAMP (0.1 micromol/l and 1.0 micromol/l) and PKIM (1.0 micromol/l) significantly (P < 0.001) inhibited the action of HCG by suppressing the increase in activin A secretion whilst preventing the decline in pro-alpha C, inhibin A and B. In addition, Rp-cAMP and PKIM were able to significantly (P < 0.05) reduce the rate of HCG-induced ovulation and meiotic resumption, but had no effect on the completion of oocyte maturation. Furthermore, HCG-induced ovulation resulted in the reduction of all three inhibin subunits, but inhibin subunit expression was not affected by Rp-cAMP and PKIM. These results provide evidence supporting a role for PKA and PKC pathways in the signalling mechanism for inhibin and activin action during ovulation and meiotic resumption of the oocyte.
authors.affiliation: Department of Reproductive Medicine, Westmead Hospital, Westmead, NSW 2145, Australia. khiemh@westgate.wh.usyd.edu.au
authors.forename: V K
authors.initials: VK
authors.lastname: Hua
authors.forename: S D
authors.initials: SD
authors.lastname: Fleming
authors.forename: P
authors.initials: P
authors.lastname: Illingworth
mesh_terms: D028341:Activins / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007265:Inhibins / Q000235:genetics* / Q000502:physiology; D008540:Meiosis; D051379:Mice; D008807:Mice, Inbred BALB C; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006080:Ovarian Follicle / Q000187:drug effects* / Q000502:physiology; D010060:Ovulation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D010062:Ovulation Induction; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D046509:Tissue Culture Techniques
chemical_list: D006063:Chorionic Gonadotropin; D017931:DNA Primers; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D028341:Activins; D007265:Inhibins; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C