Induction of ovarian cysts in progesterone-synchronized immature rats: evidence that suppression of follicular aromatase activity is not a prerequisite for the induction of cystic follicles.

Abstract

Serum hormone profiles for women and animals with cystic ovaries have led to the hypothesis that elevated serum LH and androgens are involved in the induction of ovarian follicular cysts. To test the ability of LH-like activity to induce cysts, immature rats (bearing progesterone implants to suppress endogenous LH secretion) were assigned to treatment groups that received 0 (control), 0.1, 0.5, or 1.5 IU hCG twice daily for 9 days beginning on day 27 of life. Serum progesterone concentrations were maintained at approximately 156 ng/ml throughout the in vivo treatment period. By the morning of day 36 (day 10 of treatment) the largest follicles in ovaries from control animals were at the small antral stage of development. In contrast, the largest follicles in ovaries from rats receiving 0.1, 0.5, and 1.5 IU hCG were primarily at the large antral, precystic, and cystic stages of development, respectively. On all days tested, progesterone, androstenedione, and estradiol accumulation in medium alone was greater for follicles from rats receiving hCG than for follicles from control rats. Progesterone and androstenedione increased in response to cAMP in vitro in follicular incubations from both control and hCG-treated animals. Only estradiol production by follicles from rats treated with 0.1 or 0.5 IU hCG increased in response to cAMP in vitro. Follicles from all treatment groups produced significantly more estradiol in the presence of a saturating amount of aromatizable substrate than in medium alone. Indeed, on day 36, cystic follicles produced more than 8 ng estradiol when incubated in the presence of either androstenedione or testosterone. In addition, more androstenedione was accumulated in vitro when developing cysts were incubated with exogenous testosterone than when noncystic follicles were incubated under similar conditions. The results of these experiments demonstrate that chronic stimulation by LH-like activity is capable of inducing follicular cysts in a time- and dose-related manner in intact noncycling immature rats. The ability of these cysts to produce 1-2 ng estradiol in medium alone and even greater amounts of estradiol in the presence of exogenous androgen indicates that inhibition of the ability of FSH to induce and stimulate follicular aromatase activity is not a prerequisite for the induction of follicular cysts in these animals. Finally, the increasing ability to accumulate androstenedione in the presence of exogenous testosterone suggests that follicular 17 beta-hydroxysteroid oxidoreductase activity increases in response to chronic stimulation by low doses of LH-like activity during the development of follicular cysts.