Induction of Testicular Gonadotropin-Releasing Hormone (GnRH) Receptors by GnRH: Effects of Pituitary Hormones and Relationship to Inhibition of Testosterone Production*

Abstract

In vivo administration of gonadotropin-releasinghormone (GnRH) inhibits testosterone production in intact rats and increases testicular GnRH receptors. To delineate the relationship of these effects and to determine whether GnRH induced its testicular receptor by an extrapituitary mechanism, GnRH and LH receptors were studied in intact or hypophysectomized (H) rats. Adult, H, or sham-operated (S) males were injected with GnRH (6.7 μg every 8 h for 1, 2, 4, and 6 days). Some H rats were also treated with GH and PRL (150 μg/day) to maintain LH receptors. Decapsulated testes were assayed for GnRH and LH receptors or incubated to assess testosterone production in the presence or absence of hCG. GnRH treatment in S rats resulted in a biphasic change in GnRH receptor numbers. The basal receptor concentration (212 ± 27 fmol /mg protein) increased to a peak at 2 days (501 ± 32 fmol/mg) before declining to control values after 6 days of treatment. GnRH receptors increased 2-fold 1 day after hypophysectomy (449 ± 52 fmol/mg) and were further elevated by GnRH treatment (718 ± 49 fmol/mg). Receptor concentrations remained at that level throughout the 6 days of GnRH treatment. GH and PRL administration to H rats partially inhibited the rise in GnRH receptors after hypophysectomy. This hormone treatment did not alter the GnRH-induced increase in receptors after 1 or 2 days, but decreased the response on days 4 and 6 by 63%. hCG-stimulated testosterone production was reduced by 50% on all days of GnRH treatment in S rats, while LH receptors were unchanged on the first day, but were reduced by 60% on days 2–6 of treatment. In contrast, testosterone production was only marginally inhibited after 6 days of GnRH treatment in both H and H plus GH- and PRL-treated animals, while LH s receptors were not different from control values. However, when steroidogenic responsiveness in H animals was maintained with GH, PRL, and 5 μg/day LH, testosterone production was inhibited to the same degree as in S animals after 6 days. These results indicate that GnRH can directly increase GnRH testicular receptors, but the response is modulated by anterior pituitary hormones. The decrease in LH receptors in S rats appears to be a result of increased LH secretion and not a direct effect of GnRH at the dose used. Finally, the inhibitory effect of GnRH on testosterone production is temporally dissociated from the induction of GnRH receptors and the down-regulation of LH receptors, suggesting that it is a postreceptor-mediated event.