Direct Effects of a Luteinizing Hormone-Releasing Hormone Agonist on Intratesticular Levels of Testosterone and Interstitial Fluid Formation in Intact Male Rats

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Abstract
The direct effects of an LHRH agonist (LHRH-A) on testicular interstitial fluid (IF) formation and IF levels of testosterone were studied in intact male rats aged 55-87 days. Under ether anesthesia, doses of LHRH-A ranging from 0.1-10 ng were injected into the right (R) testis, whereas the left (L) testis was injected with the injection vehicle and used to control for any peripheral effects on LHRH-A resulting from pituitary LH [lutropin] release. Overall control animals were injected in both R and L testes with vehicle alone. LHRH-A caused a significant (P < 0.001) and dose-dependent increase in levels of testosterone in IF from the R but not from the L (control) testis at 2-6 h after injection. With lower doses of LHRH-A (0.1-1 ng), this increase occurred in the absence of any increase in serum-LH levels. In contrast, injection of 10 ng LHRH-A caused sustained LH release, and although this led to a massive increase in the IF levels of testosterone in the L (control) testis, levels in IF from the R (LHRH-A injected) testis were raised significantly (P < 0.001) further. In rats injected in the R testis with 1 ng LHRH-A, the total testicular content of testosterone and the levels in blood from the R spermatic vein were also raised significantly (P < 0.001) over the corresponding levels for the lefthand side at 2 and 4 h. LHRH-A also caused dose-dependent changes in the IF volume of the R but never of the L (control) testis. Low doses (0.1-1 ng) of LHRH-A reduced the IF volume by up to 77% for up to 6 h, but when serum LH levels were raised after intratesticular injection of 10 ng LHRH-A or by peripheral injection of 50 IU hCG [human chorionic gonadotropin] LHRH-A caused an initial decrease in IF volume followed by a 60-100% increase at 4-6 h. The decrease in IF-volume and increase in IF levels of testosterone at 2 h after injection of 1 ng LHRH-A were prevented completely by injection of an LHRH antagonist together with LHRH-A. Although the increase in IF levels of testosterone induced by LHRH-A is probably due partly to the associated decrease in IF volume, the clear increase in the total testicular content of testosterone and the dissociation of changes in IF volume and its testosterone level in a number of situations suggests that LHRH-A also directly stimulates Leydig cell steroidogenesis. These studies demonstrate direct testicular effects of LHRH-A in intact rats. These effects were directed towards 2 of the fundamentally most important aspects of testicular function (IF formation, testosterone secretion) and LHRH-A interacted locally with LH (or human CG) to modify these parameters. The physiological implications of these findings with respect to local regulation of the testis by an LHRH-like peptide are discussed.

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