REGULATION OF FOLLICULAR LUTEINIZATION BY A GONADOTROPIN-RELEASING-HORMONE AGONIST - RELATIONSHIP BETWEEN STEROIDOGENESIS AND APOPTOSIS

The purpose of this study was to evaluate the effects of GnRH-analog ( Leuprolide acetate, LA) administration on follicular luteinization in equine chorionic gonadotropin plus human chorionic gonadotropin (eCG hCG)-superovulated prepubertal treated rats. Results indicate that LA treatment decreases circulating levels of progesterone (P) and P accu mulation in collagenase-dispersed ovarian cell cultures, though estrad iol (E-2) production is increased. These data suggest that cells from the LA group may be less luteinized following gonadotropin treatment. Studies performed on histological ovarian sections after different tim es of eCG administration showed that LA injections produce lower amoun ts of corpora lutea and antral follicles, and a greater number of atre tic and preantral follicles. The basal and LH-stimulated P and progest agen accumulations are decreased in incubations of corpora lutea isola ted from the LA group. In addition, the mitochondrial cholesterol side -chain cleavage (P450(scc)) levels in corpora lutea from LA-treated va ts are reduced, indicating that the decrease in P production observed is due in part to an alteration in the steroidogenic luteal capability . Immunocytochemical localization of nuclei exhibiting DNA fragmentati on by the technique of terminal deoxynucleotidyl transferase end-label ing showed that LA treatment causes an increase in the number of apopt otic cells in preantral and antral follicles at all times studied (1, 2, 4, or 7 days of LA administration). A similar effect, though less p ronounced, was observed in corpora lutea. It is concluded that LA trea tment produces a failure in the steroidogenic luteal capability and an increase of apoptotic mechanisms in the ovary, producing as a consequ ence an interference in the follicular recruitment, growth, and lutein ization induced by gonadotropins. (C) 1998 Wiley-Liss, Inc.