Obligatory Role of Luteinizing Hormone (LH) in the Initiation of Preovulatory Follicular Growth in the Pregnant Rat: Specific Effects of Human Chorionic Gonadotropin and Follicle-Stimulating Hormone on LH Receptors and Steroidogenesis in Theca, Granulosa, and Luteal Cells
The changes in serum hormone concentrations accompanying preovulatory follicular development at the end of pregnancy in the rat suggest that follicular maturation is stimulated by subtle increases in serum LH and/or by a decrease in serum progesterone but not by increases in serum FSH. To test the ability of small antral nonovulatory follicles to respond to subtle increases in LH-like activity in the presence of elevated serum progesterone, hCG (0.25 to 3.0 IU), or the control, human FSH (hFSH) (0.88 to 4.4 IU) was administered twice daily to rats on days 14 and 15 of pregnancy. hCG stimulated follicular growth, increased granulosa cell and theca cell LH receptor content, and enhanced follicular estradiol accumulation in a time-related and dose-dependent manner. Follicles from animals treated twice daily for 2 days with 1.5 IU hCG (3.5 pmol) were by day 16 functionally identical to proestrous follicles isolated on day 23, and a bolus injection of 10 IU hCG was able to induce ovulation in these hCG-primed animals. Although 35.5 pmol hFSH caused granulosa cell LH receptor content and aromatase activity to increase, hCG was clearly much more effective on a “per mole” basis in evoking these responses. FSH failed to increase either theca cell LH receptor content or the inherent ability of follicles to produce estradiol when wholly dependent on endogenous androgen substrate. In addition, 2 days of treatment with hCG caused dose-dependent decreases in LH receptor content of luteal tissue but did not alter serum concentrations of progesterone, suggesting that luteal cell progesterone production may not be associated with the luteal LH receptor response system at this time. Results of this study suggest that, even in the presence of elevated serum progesterone, sustained increases in serum LH (but not FSH) activity will support the maturation of preovulatory follicles that are functionally indistinguishable from proestrous follicles. The dependence of follicular differentiation on LH appears to involve enhancement of theca cell function and synthesis of aromatizable androgens rather than stimulation of granulosa cell aromatase activity.