LUTEINIZING-HORMONE INDUCES PROSTAGLANDIN ENDOPEROXIDE SYNTHASE-2 ANDLUTEINIZATION IN-VITRO BY A-KINASE AND C-KINASE PATHWAYS

The LH surge induces ovulation [prostaglandin synthase-2 (PGS-2)] and luteinization (progesterone synthesis) of preovulatory follicles by cA MP-dependent mechanisms. Peptides, such as GnRH and angiotensin-II, th at activate other cellular signaling pathways have been shown to mimic some of the effects of LH. Therefore, the relative functional importa nce of different cellular signaling pathways in mediating the inductio n of PGS-2 and luteinization was analyzed using the agonists (LH, GnRH , and angiotensin-II) and selective inhibitors of A-kinase (H-89), C-k inase (calphostin-C), and calmodulin kinase-II (KN93). LH or GnRH, but not angiotensin-II, markedly induced PGS-2 protein in preovulatory fo llicles. H-89 and calphostin-C, but not KN93 inhibited LH induction of PGS-2, whereas calphostin-C selectively blocked induction by GnRH. In contrast, the A- and C-kinase inhibitors prevented both LH and GnRH i nduction of granulosa cell luteinization. Taken together, these result s provide biological evidence that the response of granulosa cells to the LH surge appears to involve the activation of A- and C-kinase path ways.