Factors determining whether the direct effects of an LHRH agonist on Leydig cell function in vivo are stimulatory or inhibitory.

The influence of (1) repeated exposure to LHRH agonist and (2) concomitant exposure to various levels of LH or hCG, on the direct testicular effects of LHRH agonist have been investigated in hypophysectomized and intact rats. In the latter, LHRH agonist was injected intratesticularly into the right testis whilst the left testis was injected with vehicle, and the level of testosterone in interstitial fluid (IF) from left and right testes was compared 2-4 h later. In hypophysectomized rats, a single injection of 50-1000 ng LHRH agonist raised (P less than 0.001) serum levels of testosterone 2 h later to within the normal range (1-8 ng/ml) for intact rats of comparable age. Subsequent daily injections of LHRH agonist elicited progressively smaller responses and by day 5 no response was evident, this decline being unrelated to the increase in time after hypophysectomy. Comparable changes were observed in hypophysectomized rats pretreated with an LH antiserum. Daily injection of hypophysectomized rats with 10 IU hCG for 6 days raised serum levels of testosterone to supraphysiological levels on each day, whilst concomitant injection of LHRH agonist (1 microgram) decreased (P less than 0.001) this response at all times, an effect that became progressively more pronounced. In contrast, daily treatment with 1 microgram ovine LH raised serum levels of testosterone to within the physiological range, and concomitant treatment with LHRH agonist (50 ng) had either no effect (days 1-2) or significantly increased (days 4-6) the testosterone response to LH. In intact rats, a single unilateral intratesticular injection of 1 ng LHRH agonist increased the IF levels of testosterone unilaterally 3 h later, but subsequent injections on days 2 and 3 elicited progressively smaller responses. In rats given a single intratesticular injection of LHRH agonist combined with a peripheral injection of different doses of LH or hCG, the LHRH agonist induced a unilateral increase in IF levels of LH/hCG, whilst in rats treated with high doses of LH (12.5--25 micrograms) or hCG (50 IU). LHRH agonist either had no effect or significantly reduced the IF levels of testosterone unilaterally. However, LHRH agonist also had significant effects on testicular IF volume and, as this may reflect altered transport of LH and hCG to the Leydig cells, the inhibitory effects of LHRH agonist may be related to this change rather than to an effect of steroidogenesis itself.(ABSTRACT TRUNCATED AT 400 WORDS)