Effects of Human Chorionic Gonadotropin and Progesterone on Follicular Development in the Immature Rat*

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Abstract
To determine if small sustained increases in serum LH (hCG) activity can stimulate the maturation of small antral follicles in intact prepubertal rats, 24- or 29-day-old animals were injected twice daily for 2 days with 0.15 IU hCG. Functional changes in follicular cells were determined by measuring granulosa and thecal cell LH/hCG receptor content, follicular arornatase activity, endogenous estradiol production, and hormonally responsive progesterone accumulation, prostaglandin production, and adenylate cyclase activity in vitro. Each of these follicular components or activities increased progressively after the administration of 0.15 IU hCG in vivo. A bolus injection of 5 IU hCG induced ovulation in these low dose hCGtreated animals, with an average of 11 ovulations/rat, indicating that preovulatory follicles had developed. To determine if physiological concentrations of serum progesterone have an effect on the responsiveness of small antral follicles to hCG, progesterone implants (delivering 50–70 ng/ml) were inserted sc in 27-day-old rats, and increasing doses of hCG (0.015 to 0.3 IU) were injected on days 29 and 30. Estradiol accumulation by follicles from untreated 29-day-old rats bearing progesterone implants was less than that in similar rats without implants and was associated with lower serum LH concentrations. Thus, it was surprising to observe that elevated serum progesterone appeared to enhance the response of follicles to the lowest doses of hCG (0.015 and 0.05 IU) administered in vivo. Both follicular estradiol accumulation and aromatase activity increased in a dose-dependent manner in response to 0.015 and 0.05 IU hCG in rats with implants but failed to do so in animals without implants. In addition, after treatment with hCG in vivo, progesterone accumulation in vitro in response to hCG was also greater for follicles from rats with implants than for those from rats without implants. hCG- and FSH-stimulated prostaglandin production in vitro were also increased by treatment with hCG in vivo, but were not markedly affected by the presence of high serum concentrations of progesterone. These results suggest 1) that sustained increases in serum LH (hCG) activity can stimulate the growth of small antral follicles to preovulatory follicles in the intact prepubertal rat, and 2) that elevated, but physiological, concentrations of serum progesterone can act to enhance rather than inhibit the response of small antral follicles to low concentrations of exogenous hCG. Thus, in situations in which basal LH is low (such as at puberty, during the estrous cycle, and in early pregnancy), progesterone may facilitate the effects of LH and support the growth of small antral follicles to the preovulatory stage.

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