Ovarian Gonadotropin-Releasing Hormone (GnRH) Receptors: Characterization, Distribution, and Induction by GnRH*

Gonadotropin-releasing hormone (GnRH) and its analogs have direct extrapituitary effects on the gonads to inhibit steroidogenesis. In the present study, the nondegradable GnRH analog [125I]D-Alaa-des-Gly10-GnRH ethylamide is shown to specifically bind to ovarian, testicular, and adrenal membrane preparations. The ovarian GnRH receptor has a binding affinity similar to that of the anterior pituitary receptor and is specific for GnRH and GnRH analogs. The GnRH-binding capacity of whole ovarian membrane preparations is 150 fm/mg protein, 3- to 4-fold lower than that of anterior pituitary membranes. The number or affinity of receptors prepared from whole ovarian tissue is not influenced by the time of day, stage of the estrous cycle, or hypophysectomy. However, the GnRH receptor concentration is higher in follicular (371 ± 43 fmol/mg) than luteal (162 ± 25 fmol/mg) membranes from cycling rats. Since GnRH injections increase the number of GnRH receptors in the pituitary, the effect of GnRH on ovarian GnRH binding was studied. GnRH (20 μg/day, sc, every 8 h for 3 days) had no effect on the affinity or capacity of ovarian tissue of cycling rats, but the GnRH receptor concentration doubled in whole ovarian and luteal tissue if injections were initiated on day 15 of pregnancy. GnRH binding to membranes from functionally active granulosa cells was examined in immature hypophysectomized (H) rats treated with 17β-estradiol (E) for 3 days (HE3) or with E, followed by FSH (F) for 2 days (HE3F2). The GnRHbinding capacities of granulosa cell tissue from both HE3 and HE3F2 rats are similar to that of follicular tissue of cycling rats. GnRH injections (4.0 or 40 μg/day, sc, every 8 h for 3 days) resulted in a 2-fold increase in the number of receptors on granulosa cell tissue from HE3F2 but not HE3 rats. Specific receptors for GnRH are present in the ovary and follicular tissue has a higher concentration of GnRH receptors than luteal tissue. GnRH increases its own receptors in follicular or luteal tissue which is functionally active, suggesting that an increase in GnRH binding may be involved in the inhibition of steroidogenesis. The presence and precise role of GnRH or a GnRH-like peptide in the ovary remain uncertain and awaits further study.