| First Author | Zhu L | Year | 2010 |
| Journal | Biochem J | Volume | 432 |
| Issue | 3 | Pages | 473-83 |
| PubMed ID | 21108604 | Mgi Jnum | J:167044 |
| Mgi Id | MGI:4867097 | Doi | 10.1042/BJ20100460 |
| Citation | Zhu L, et al. (2010) PPARgamma co-activator-1alpha co-activates steroidogenic factor 1 to stimulate the synthesis of luteinizing hormone and aldosterone. Biochem J 432(3):473-83 |
| abstractText | The orphan nuclear receptor SF-1 (steroidogenic factor 1) is highly expressed in the pituitary, gonad and adrenal glands and plays key roles at all levels of the hypothalamic-pituitary-steroidogenic tissue axis. In the present study, we show that PGC-1alpha [PPARgamma (peroxisome-proliferator-activated receptor gamma) co-activator 1alpha] interacts with and co-activates SF-1 to induce LHbeta (luteinizing hormone beta) and alphaGSU (alpha-glycoprotein subunit) gene expression, subsequently leading to the increased secretion of LH in pituitary gonadotrope-derived alphaT3-1 cells. PGC-1alpha co-activation of LHbeta expression requires an SF-1-binding element [GSE (gonadotrope-specific element)] mapped to the promoter region of LHbeta. Mammalian two-hybrid and co-immunoprecipitation assays, as well as GST (glutathione transferase) pull-down experiments demonstrated that PGC-1alpha interacts with SF-1 in vivo and in vitro. Additionally, PGC-1alpha stimulates the expression of Cyp11b2 (aldosterone synthase gene), Cyp11b1 (steroid 11beta-hydroxylase gene) and P450scc (cholesterol side-chain cleavage enzyme), and the synthesis of aldosterone in adrenal-cortex-derived Y-1 cells. Chromatin immunoprecipitation assays confirmed that endogenous PGC-1alpha co-localizes with SF-1 in the LHbeta and Cyp11b2 promoter region. Knockdown of endogenous SF-1 by siRNA (small interfering RNA) abolished the PGC-1alpha induction of LHbeta and Cyp11b2 gene expression in alphaT3-1 and Y-1 cells respectively. Finally, we demonstrated that PGC-1alpha induces SF-1 gene expression in both alphaT3-1 and Y-1 cells. Taken together, our findings reveal the potential role of PGC-1alpha and suggest that it may play important roles in steroidogenesis, gonad development and sex differentiation through SF-1. |
