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

The effects of interleukin-1β (IL-1β) on the secretory activity of Leydig cells were investigated in hypophysectomized/human chorionic gonadotropin (hCG)-treated rats. IL-1β dose-dependently increased basal and hCG-stimulated plasma testosterone concentration (PTC) and testosterone secretion by isolated Leydig cells. Basal PTC returned to the control level 12 h after the injection of a maximal effective dose of IL-1β (10 nmol/rat), but after 24 and 36 h it was markedly lower than in control animals; after 48 h PTC again attained the control value. IL-1β did not affect basal PTC in rats injected 24 h before with 10 nmol of IL-1β (IL-1β-pretreated rats), but it dose-dependently decreased hCG-stimulated PTC. However, IL-1β dose-dependently enhanced both basal and hCG-stimulated testosterone production by dispersed Leydig cells obtained from IL-1β-pretreated rats. Corticotropin-releasing hormone (CRH) concentration was very low in the testes of control rats, but it did display a striking rise 24 h after the injection of IL-1β. As expected, CRH (100 pmol/rat) and IL-1β (10 nmol/rat) elicited a marked decrease in hCG-enhanced PTC in IL-1β-pretreated rats. (a-Helical)-CRH, a competitive inhibitor of CRH, did not alter hCG-stimulated PTC in control IL-1β-pretreated rats, but it did completely annul the inhibitory effect of both CRH and IL-1β. In light of the present findings, it seems reasonable to suggest that IL-1β exerts a two-fold modulatory action on rat testis steroidogenesis: IL-1β (i) acutely stimulates testosterone secretion by acting directly on Leydig cells, and (ii) induces the intratesticular production 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.