Molecular Regulation of Genes Involved in Ovulation and Luteinization

Two principal physiological events occur within preovulatory follicles as a consequence of the LH/FSH surge: ovulation and luteinization. The ovulation process culminates in the extrusion of the oocyte-cumulus complex and is dependent on a specific sequence of biochemical events. These biochemical changes include the rapid but transient increase in a novel, distinct isoform of prostaglandin endoperoxide synthase (PGS-2) (1–8), tissue plasminogen activator (tPA) (9, 10), and progesterone receptor (PR) (11–13). In contrast, luteinization is a process by which follicular granulosa and theca cells become nonmitotic and establish a specific, stable luteal cell phenotype. The biochemical changes that occur in response to the LH surge and are associated with luteinization include the marked and sustained induction of cholesterol side-chain cleavage cytochrome P450 (P450scc), as well as the dramatic and rapid decreases in mRNA for the LH receptor (LH-R), the regulatory subunit β of type II cyclic AMP-dependent protein kinase (RIIβ), aromatase, and 17α-hydroxylase (P45017α) (Fig. 10.1) (14). Once luteinization has occurred, genes regulated by FSH/LH/cAMP in the follicle are no longer regulated by these agonists in the corpus luteum. This apparent transition from cAMP-dependent regulation to cAMP-independent regulation of these genes has prompted us to ask why surge (as opposed to basal) concentrations of LH are required to initiate these two diverse processes, what might be unique about the genes induced by the LH surge, and what intracellular signaling pathways might be involved.