EFFECTS OF INTERLEUKIN-1-BETA ON STEROIDOGENESIS IN LEYDIG-CELLS OF THE RAT TESTIS - IN-VIVO AND IN-VITRO STUDIES

The effects of interleukin-1beta (IL-1beta) on the secretory activity of Leydig cells were investigated in hypophysectomized/human chorionic gonadotropin (hCG)-treated rats. IL-1beta dose-dependently increased basal and hCG-stimulated plasma testosterone concentration (PTC) and t estosterone secretion by isolated Leydig cells. Basal PTC returned to the control level 12 h after the injection of a maximal effective dose of IL-1beta (10 nmol/rat), but after 24 and 36 h it was markedly lowe r than in control animals; after 48 h PTC again attained the control v alue. IL-1beta did not affect basal PTC in rats injected 24 h before w ith 10 nmol of IL-1beta (IL-1beta-pretreated rats), but it dose-depend ently decreased hCG-stimulated PTC. However, IL-1beta dose-dependently enhanced both basal and hCG-stimulated testosterone production by dis persed Leydig cells obtained from IL-1beta-pretreated rats. Corticotro pin-releasing hormone (CRH) concentration was very low in the testes o f control rats, but it did display a striking rise 24 h after the inje ction of IL-1beta. As expected, CRH (100 pmol/rat) and IL-1beta (10 nm ol/rat) elicited a marked decrease in hCG-enhanced PTC in IL-1beta-pre treated rats. (alpha-Helical)-CRH, a competitive inhibitor of CRH, did not alter hCG-stimulated PTC in control IL-1beta-pretreated rats, but it did completely annul the inhibitory effect of both CRH and IL-1bet a. In light of the present findings, it seems reasonable to suggest th at IL-1beta exerts a two-fold modulatory action on rat testis steroido genesis: IL-1beta (i) acutely stimulates testosterone secretion by act ing directly on Leydig cells, and (ii) induces the intratesticular pro duction of CRH, which in turn inhibits Leydig-cell secretory activity. This last effect, however, requires 24 h to become manifest, since it probably involves the de novo expression of CRH gene.