INTERLEUKIN-1 INDUCES INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 GENE-EXPRESSION AND PROTEIN-PRODUCTION BY LEYDIG-CELLS

Interleukin-1 (IL-1) is a potent inhibitor of Leydig cell function. IL -1 blocks human CG-induced cAMP and testosterone formation, as well as cytochrome P450 side-chain cleavage messenger RNA (mRNA) expression. IL-1 also decreases insulin-like growth factor-I (IGF-I) mRNA levels i n Leydig cells. The effects of IGF-I are modified by IGF binding prote ins (IGFBPs). In the present study, we evaluated the effects of IL-1 o n IGFBP expression. Purified Leydig cells from adult rats were culture d with 0.1% heat-inactivated fetal bovine serum in Dulbecco's modified Eagles' medium/F12. Culture medium was changed to serum-free Dulbecco 's modified Eagles' medium/F12 after 24 h and IL-1 beta (0.1-10 ng/ml) was added. Treatment of Leydig cells with IL-1 beta (10 ng/ml) for 2, 4, and 6 h resulted in a progressive induction of IGFBP-3 expression without affecting IGFBP-2 or IGFBP-4 mRNA levels. IL-1 beta in concent rations of 0.1, 1, and 10 ng/ml caused a 1.5-, 4-, and 6.5-fold induct ion of IGFBP-3 expression,