DIFFERENTIAL-EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1ON 3-BETA-HYDROXYSTEROID DEHYDROGENASE DELTA(5)-]DELTA(4) ISOMERASE EXPRESSION IN MOUSE LEYDIG-CELLS

Immune-endocrine interactions are important to the regulation of Leydi g cell steroidogenesis, We have shown previously that both tumor necro sis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1-beta) inhibi t 8-bromo-cAMP-(8-Br-cAMP)-stimulated steroidogenesis in mouse Leydig cells. TNF and IL-1 both inhibit cAMP-stimulated testosterone producti on as well as mRNA and protein levels of cholesterol side chain cleava ge enzyme (P450scc) and 17 alpha-hydroxylase/C-17,C-20 lyase (P450c17) in mouse Leydig cells, Neither TNF nor IL-1 affects basal levels of P 450scc mRNA and protein. In the present study, we tested the effects o f TNF and IL-1 on basal testosterone production and 8-Br-cAMP-stimulat ed 3 beta-hydroxysteroid dehydrogenase/Delta(5)-->Delta(4) isomerase ( 3 beta HSD) expression in Leydig cells. Purified and macrophage-deplet ed Leydig cells were cultured for 5 d with daily changes of media, and then treated with increasing concentrations of recombinant mouse TNF or IL-1 in the presence or absence of 8-Br-cAMP (50 mu M) for 24 h, Th e media were collected for testosterone RIA and RNA and protein were e xtracted from cells. Basal testosterone production was inhibited by TN F, but not IL-1, Treatment of Leydig cells with 8-Br-cAMP alone caused a marked increase in 3 beta HSD mRNA, and protein levels. Both TNF an d IL-1 inhibited cAMP-stimulated 3 beta HSD mRNA and protein levels, b ut only TNF inhibited basal 3 beta HSD expression. These results demon strate that TNF and IL-1 have different effects on basal steroidogenes is in Leydig cells and suggest that TNF-mediated inhibition of basal t estosterone production may be owing to the inhibition of basal 3 beta- HSD expression in Leydig cells.