INDUCTION OF OVARIAN FOLLICULAR CYSTS IN THE PREGNANT RAT BY HUMAN CHORIONIC-GONADOTROPIN

Prolonged stimulation by human chrorionic gonadotropin (hCG) induce ovarian follicular cysts in progesterone-synchronized immature rats [Bogovich, Endocrinology 1989; 124:1646-1653]. To determine if unabated stimulation by hCG has a similar effect on follicular development in adult ovaries, pregnant rats were given either 0 (control), 1, or 3 IU hCG twice daily for 9 days beginning on Day 13 of pregnancy. By Day 22 of pregnancy, rats treated with 1 IU hCG possessed large antral follicles at least 1 mm in diameter: approximately 33% larger than the diameters of preovulatory follicles observed in control rats (0 IU hCG). In contrast, rats treated with 3 IU hCG displayed ovarian follicular cysts up to 5 mm in diameter, with well-developed thecae and just a remnant of granulosa cells. Progesterone, androstenedione, and estradiol accumulation was greater in follicular incubates from hCG-treated rats than in incubates from control rats. Progesterone increased in response to cAMP in incubates from all treatment groups on all days tested. Androstenedione increased in response to cAMP on Day 22 of pregnancy for follicles from control animals, on all days tested for follicles from rats treated with 1 IU hCG, and on Days 15-19 for follicles from rats treated with 3 IU hCG. Androstenedione production in the presence of 300 ng of exogenous testosterone was significantly greater in follicular incubates from animals treated with 1 and 3 IU hCG than incubates from control animals on Days 19-22 of pregnancy. Estradiol production increased in response to cAMP on Day 22 of pregnancy for follicles from control rats and on Days 17-19 for follicles from rats treated with 1 IU hCG, but failed to increase for follicles/cysts from rats treated with 3 IU hCG. In contrast, the capacity of follicles/cysts from rats treated with 3 IU hCG to produce estradiol in the presence of exogenous testosterone was as great as that observed for preovulatory follicles from control rats on Day 22 of pregnancy. The ability of hCG to induce follicular cysts in the highly differentiated ovaries of pregnant rats strongly suggests that the fundamental mechanisms involved in cyst development in this species do not depend on the differentiated/development state of the ovary. Instead, the data support the concept that prolonged stimulation by LH-like activity without interruption by a gonadotropin surge, rather than the degree to which serum LH concentrations may be elevated, is critical for the development of ovarian follicular cysts.