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 preantal 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 μmol/l and 1.0 μmol/l) and PKIM (1.0 μmol/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.