Enhancement and desensitization of hormone-responsive adenylate cyclase in granulosa cells of preantral and antral ovarian follicles: effects of estradiol and follicle-stimulating hormone.

The present study was performed to determine if adenylate cyclase in granulosa cells was affected by the pituitary hormone FSH and the ovarian hormone estradiol. Results demonstrate that granulosa cells of intact immature rats exhibit considerably more FSH- than hCG-stimulated adenylate cyclase activity. The FSH-responsive enzyme system was not altered by hypophysectomy or by treating hypophysectomized rats with FSH alone, but was increased slightly by treatment with estradiol alone. Sequential treatment of rats with estradiol and FSH markedly increased both FSH- and LH/hCG-stimulated adenylate cyclase activities. Thus, FSH-responsive adenylate cyclase appears to be a constitutive component of granulosa cells in prenatal follicles which exhibits a pronounced increase during the development of preovulatory follicles, a change dependent on the synergistic actions of estradiol and FSH. Desensitization of FSH-responsive adenylate cyclase in granulosa cells of preantral and antral follicles was assessed by administering 5 micrograms human FSH to estradiol or estradiol/FSH-treated rats, respectively. FSH failed to induce desensitization of adenylate cyclase in granulosa cells of preantral follicles at 2 h, but did desensitize the enzyme system in granulosa cells of antral follicles. Furthermore, the desensitization of adenylate cyclase in granulosa cells of antral follicles was heterologous; both FSH and hCG exerted this effect. The causes of the differences in the response of adenylate cyclase to high concentrations of FSH at different stages of follicular development remain unclear. The absence of desensitization in preantral follicles may be required to permit a continuous nondisruptive pattern of follicular growth when small follicles are repeatedly exposed to gonadotropin surges, whereas desensitization is required for the cessation of follicular growth and luteinization.