XXXX induces insulin-like growth factor binding protein-3 gene expression and protein production by Leydig cells.

@entity1 @entity268 @entity251 @entity12561 @entity1356 @entity2301 @entity1880 @entity442 @entity10513 @entity1192 @entity35
@entity1192 ( @entity1192 ) is a potent inhibitor of Leydig cell function. @entity1192 blocks @entity1 CG-induced @entity268 and @entity251 formation, as well as cytochrome P450 side-chain cleavage messenger RNA (mRNA) expression. @entity1192 also decreases insulin-like growth factor-I ( @entity442 ) mRNA levels in Leydig cells. The effects of @entity442 are modified by IGF binding proteins (IGFBPs). In the present study, we evaluated the effects of @entity1192 on IGFBP expression. Purified Leydig cells from adult @entity35 were cultured 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 @entity1356 (0.1-10 ng/ml) was added. Treatment of Leydig cells with @entity1356 (10 ng/ml) for 2, 4, and 6 h resulted in a progressive induction of @entity2301 expression without affecting @entity10513 or @entity12561 mRNA levels. @entity1356 in concentrations of 0.1, 1, and 10 ng/ml caused a 1.5-, 4-, and 6.5-fold induction of @entity2301 expression, respectively, whereas @entity442 mRNA levels were decreased in a dose-dependent manner. @entity1356 increased the average transcription rate of @entity2301 by 3.3-fold. The t1/2 for @entity2301 mRNA was 2.07 h and was not affected by the treatment with @entity1356 (2.21 h). The immunoblot of cell-conditioned media showed that the basal level of @entity2301 protein was low and @entity1356 caused a dose-dependent increase in the production of @entity2301 . These results indicate that @entity1356 increases @entity2301 levels by increasing the rate of transcription rather than by changing the stability of @entity2301 mRNA. The addition of @entity1880 markedly inhibited @entity1356 -induced @entity2301 mRNA levels. However, @entity1356 was able to induce @entity2301 mRNA levels even in the presence of @entity1880 . This suggests that de novo protein synthesis may not be required for induction of @entity2301 mRNA by @entity1356 . In conclusion, @entity1356 inhibits @entity442 but increases @entity2301 expression in Leydig cells, and this may contribute to the inhibitory effects of @entity1356 on Leydig cell steroidogenesis.
