Age-dependent stimulation of Leydig cell steroidogenesis by interleukin-1 isoforms

Different isoforms of testicular interleukin-1 (IL-1) were analysed to determine whether there were differences in the ability to modulate rat Leydig cell steroidogenesis in vitro. Rat 17K IL-1 alpha and 1L-1 beta, 32K IL-1 alpha precursor (32proIL-1 alpha) and a 24K splice variant (24proIL-1 alpha) stimulated testosterone production by Leydig cells from 40- but not 80-day-old rats. The potency of the isoforms was IL-1 alpha >IL-1 beta > 32proIL-1 alpha >24proIL-1 alpha, IL-1 alpha being 50-fold more potent than IL-1 beta. IL-1 receptor antagonist reversed the effects and IL-1 receptor type 1 mRNA was expressed by the responding Leydig cells, indicating a receptor mediated action. Inhibition of PKA and Ca2+ channels abolished IL-1-induced steroidogenesis, while inhibition of PKC had no significant effect. Except for 24proIL-1 alpha which was stimulatory, all IL-1 isoforms suppressed hCG-driven testosterone production. This inhibitory effect was abolished by androstendione, suggesting that P450c17 was suppressed by IL-1. Our results indicate that IL-1 plays a paracrine role in the regulation of Leydig cell steroidogenesis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.