HDAC7 modulates TNF-α-mediated suppression of Leydig cell steroidogenesis.

Abstract

The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) has an inhibitory role in gonadal functions particularly in the steroidogenesis of Leydig cells. In the present study, we demonstrate that TNF-α activates histone deacetylases 7 (HDAC7), which regulates the expression of steroidogenic enzyme genes in Leydig cells. LC-540 Leydig cells were treated with TNF-α (10 ng/ml) for different time intervals. TNF-α treatment significantly suppressed histone H3 acetylation and methylation and, concomitantly, increased the total histone deacetylases activity in LC-540 Leydig cells. RT-PCR and western blot analysis revealed that HDAC7 was up-regulated in TNF-α-treated cells. Our results also demonstrated that an siRNA-mediated knockdown of HDAC7 restores the expression of steroidogenic proteins in TNF-α-treated Leydig cells. These findings provide valuable information that TNF-α-mediated suppression of steroidogenesis involves HDAC7 in Leydig cells.