LH stimulates a rapid cAMP-mediated, gap junction-dependent activation of PDE3A in oocytes

A major regulator of the intraoocyte levels of cAMP is the cGMP-inhibited PDE3A. This oocyte-specific PDE hydrolyses cAMP, counterbalancing its autonomous GPR3 production and gap junctional transfer from the follicle soma. The pituitary luteinizing hormone (LH) induces resumption of meiosis by reducing the somatic cGMP, which in concomitance with closure of gap junctions lowers its availability to the oocyte. Nevertheless, unlike cGMP, LH elevates the follicle cAMP. This apparent paradox questions whether and how the somatic cAMP elevation serves reinitiation of meiosis. To challenge this intriguing option, we used rat ovarian follicle clusters and cumulus-enclosed/cumulus-free, fully-grown oocytes. The oocytes were incubated with dbcAMP to elevate their cAMP. Follicles were incubated with LH to induce resumption of meiosis. Participation of NO-iNOS pathway was evaluated by either the NO-donor, SNAP or the iNOS inhibitor AG, and involvement of cGMP by a selective sGC inhibitor, ODQ. At the end of incubations, PDE3A activity as well as cAMP concentrations within oocytes were determined. We detected a LH-induced immediate elevation of intra-oocyte cAMP, followed by PKA-mediated activation of PDE3A. Both events were depended on open gap junctions. At this time window, the LH-induced decrease in granulosa-cells NO production followed by reduction in cGMP contributed to the relief of PDE3A inhibition. The later termination of cell-to-cell communication backed a sustained PDE3A activity by stopping the transfer of both, cAMP and cGMP. Our present study suggests that the transient increase in intraoocyte cAMP, which activates the oocyte PDE3A, may serve as a complementary mechanism, to increase the efficiency of LH-induced oocyte maturation.