Regulation of follicular luteinisation by a gonadotropin-releasing hormone agonist: relationship between steroidogenesis and apoptosis

摘要

To study the effects of the GnRH analogue, leuprolide acetate (LA), on luteal function in superovulated rats, LA or vehicle (controls) was given to rats superovulated with equine chorionic gonadotropin (eCG) + HCG. LA treatment decreased circulatinglevels of progesterone and progesterone accumulation in collagenase-dispersed ovarian cell cultures (14.41 vs. 79.81 ng/ml in controls; P<0.05), but oestradiol production was increased, suggesting that cells from the LA group may be less luteinized after gonadotropin treatment. Histological examination of ovarian sections taken at different times after eCG administration showed that LA-treated animals produced fewer corpora lutea and antral follicles and more atretic and preantral follicles than controls. The basal and LH-stimulated progesterone and 20alpha-hydroxy-progesterone accumulations were decreased in incubations of corpora lutea isolated from the LA group. The mitochondrial cholesterol side-chain cleavage (P450SCC)>) levels in corpora lutea from LA-treated rats were also reduced, indicating that the decrease in progesterone production observed is due in part to alterations in steroidogenic luteal capability. Immunocytochemical localization of nuclei exhibiting DNA fragmentation by terminal deoxynucleotidyl transferase end-labelling showed that LA treatment caused an increase in the number of apoptotic cells in preantral and antral follicles at all times studied (1, 2, 4 and 7 days after LA administration). A similar effect, though less pronounced, was observed in corpora lutea. It is concluded that LA treatment produces a failure in the steroidogenic luteal capability and an increase in apoptotic mechanisms in the ovaries. Consequently, there is an interference in follicular recruitment, growth and luteinization induced by gonadotropins.