Inhibin increases and progesterone decreases receptors for gonadotropin-releasing hormone in ovine pituitary culture.

Treatments (48 h) with highly purified bovine or porcine inhibins (10 ng/ml) induced ovine pituitary cells to increase their binding for des-Gly10-[D-Ala6]LHRH-ethylamide by 3.6- and 5-fold, respectively. Studies with less pure inhibin from porcine follicles showed that increased binding could reach 7-fold within 48 h and was due to higher numbers of receptors for GnRH. The 48-h increase in GnRH receptors was linear with time and was rapidly reversible, since removal of inhibin at 24 h decreased GnRH binding below control levels at 48 h. Inhibin (bovine or porcine) also increased GnRH-stimulated secretion of LH by 2-fold. The ED50 for both inhibin actions noted above was in the range of 0.5-2.0 ng/ml (in terms of highly purified bovine inhibin). Progesterone (P) totally counteracted inhibin induction of GnRH binding and GnRH-stimulated LH secretion at 48 h. In the absence of inhibin, P decreased GnRH binding below control levels by as much as 80% within 48 h, but did not affect GnRH-stimulated LH secretion at 48 h. The ED50 for P action was near 1 nM, which is within the physiological range for P during the luteal phase of the sheep estrous cycle. The data suggest that P may act during the luteal phase to decrease receptors for GnRH. The rapid decrease in P during the 48 h before the preovulatory LH surge should permit GnRH receptors to rise under the influence of inhibin (and estradiol) to boost gonadotroph responsiveness to GnRH so the LH surge may occur to its fullest.