FOLLICULAR DEVELOPMENT, STEROIDOGENESIS AND GONADOTROPIN-SECRETION IN RESPONSE TO LONG-TERM TREATMENT WITH A GONADOTROPIN-RELEASING-HORMONE AGONIST IN THE RAT

Gonadotrophin-releasing hormone (GnRH) and its agonists are implicated in the local control of rat ovarian function. We have evaluated the effects of long-term administration of different doses of GnRH agonist (GnRH-Ag) in vivo (a) on reproductive cyclicity and follicular development, (b) on peripheral gonadotrophin and steroid concentrations and (c) on in vitro cAMP and progesterone production by the follicles in response to stimulatory doses of FSH or LH (1 mu g/ml). GnRH-Ag (0.2, 1 or 5 mu g/day) administration for 28 days had a profound impact on the oestrous cycle of rats as revealed by vaginal cytology. GnRH-Ag treatment caused a decrease in ovarian and uterine weights, which correlated very well with the decrease in the number of follicles present in the ovary. GnRH-Ag (5 mu g/day) reduced the number of early preantral follicles and there was complete disappearance of early as well as late antral follicles. However, a dose of 1 mu g GnRH-Ag/day was effective in the complete demise of only late antral follicles with a significant attenuation in the number of early antral follicles. There was an enhancement in serum LH concentrations in response to the highest dose of GnRH-Ag administration with serum FSH concentrations declining in rats treated with the two higher doses. However, serum prolactin concentrations were attenuated only in rats treated with the highest dose of GnRH-Ag. GnRH-Ag treatment decreased serum progesterone and oestradiol concentrations. Preantral follicles obtained from the rats treated with 0.2 or 1 mu g GnRH-Ag/day resulted in an attenuated response to LH- or FSH-stimulated progesterone production, whereas antral follicles showed an exaggerated response to the stimulatory doses of FSH in vitro. Antral follicles obtained from the rats treated with 0.2 mu g/day showed a robust decrease in cAMP accumulation in response to LH with a slight decrease only with FSH. In contrast, preantral follicles obtained from GnRH-Ag-treated rats did not show any significant attenuation in cAMP production. These data suggest that GnRH-Ag exerts a direct inhibitory effect on follicular development and steroidogenesis and as a result it interferes with the normal oestrous cyclicity in the rat.