Interleukin-1 alpha-induced changes in androgen and cyclic adenosine 3',5'-monophosphate release in adult rat Leydig cells in culture.

Interleukin-1 (IL-1) has been proposed as a paracrine regulator of testicular function. The effect of this cytokine on adult rat Leydig cells in primary culture was investigated. Interstitial cells were purified on a two-step Percoll gradient and cultured in the presence or absence of recombinant human IL-1 alpha (IL-1 alpha). The presence of IL-1 alpha in the culture media resulted in a dose-dependent increase in 24-h basal androgen release (half-maximal effective concentration = 40-50 U/ml). The stimulatory effect of IL-1 alpha peaked on days 3 and 4, and was often still significant after 6 days of culture. Removal of IL-1 alpha was followed by a return of basal androgen release to control levels within 3 days. In contrast, cells treated with IL-1 alpha (100 U/ml) for 3 days released significantly less androgen (per 4 h) in response to 1-100 ng LH/ml than control cells. A similar inhibitory effect on the response to dibutyryl cAMP and pregnenolone was observed. Under basal conditions, IL-1 alpha-treated cells released significantly more cAMP than did control cells. In contrast, the increase in cAMP release seen with LH-stimulated cells was significantly inhibited by treatment with IL-1 alpha. These results suggest that IL-1 alpha has a dual effect on adult rat Leydig cells in culture. It stimulates basal but inhibits LH-induced androgen release with parallel changes in cAMP levels. An additional inhibitory effect appears to lie at the level of the 17 alpha-hydroxylase/C17-20 lyase enzyme.