Molecular mechanism of suppression of testicular steroidogenesis by proinflammatory cytokine tumor necrosis factor alpha.

ABSTRACT: Tumor necrosis factor alpha (TNF-alpha) has been demonstrated to inhibit steroidogenesis in Leydig cells at the transcriptional level of steroidogenic enzymes. However, the molecular mechanism of this observed gene repression is not well understood. We now demonstrate that nuclear factor kappaB (NF-kappaB) activated by TNF-alpha inhibits the transactivation of orphan nuclear receptors, which regulate the expression of steroidogenic-enzyme genes. TNF-alpha treatment suppressed the luteinizing-hormone-induced or Nur77/SF-1-stimulated promoter activity of steroidogenic-enzyme genes in Leydig cells. The TNF-alpha-mediated gene suppression was blocked by treatment with an inhibitor of NF-kappaB. In addition, overexpression of the p65 (RelA) subunit of NF-kappaB showed the same effect as TNF-alp

SUBMITTER: Hong CY 

PROVIDER: S-EPMC371106 | biostudies-literature | 2004 Apr

REPOSITORIES: biostudies-literature