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

Abstract

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-1α and IL-1β, 32K IL-1α precursor (32proIL-1α) and a 24K splice variant (24proIL-1α) stimulated testosterone production by Leydig cells from 40- but not 80-day-old rats. The potency of the isoforms was IL-1α>IL-1β>32proIL-1α>24proIL-1α, IL-1α being 50-fold more potent than IL-1β. IL-1 receptor antagonist reversed the effects and IL-1 receptor type I mRNA was expressed by the responding Leydig cells, indicating a receptor mediated action. Inhibition of PKA and Ca 2+ channels abolished IL-1-induced steroidogenesis, while inhibition of PKC had no significant effect. Except for 24proIL-1α 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.