| First Author | Park E | Year | 2014 |
| Journal | Mol Endocrinol | Volume | 28 |
| Issue | 6 | Pages | 822-33 |
| PubMed ID | 24725081 | Mgi Jnum | J:214680 |
| Mgi Id | MGI:5603689 | Doi | 10.1210/me.2013-1150 |
| Citation | Park E, et al. (2014) Differential regulation of steroidogenic enzyme genes by TRalpha signaling in testicular Leydig cells. Mol Endocrinol 28(6):822-33 |
| abstractText | Thyroid hormone signaling has long been implicated in mammalian testicular function, affecting steroidogenesis in testicular Leydig cells. However, its molecular mechanism is not well understood. Here, we investigated the molecular action of thyroid hormone receptor-alpha (TRalpha) on mouse testicular steroidogenesis. TRalpha/thyroid hormone (T3) signaling differentially affected the expression of steroidogenic enzyme genes, mainly regulating their promoter activity. TRalpha directly regulated the promoter activity of the cytochrome P450 17alpha-hydroxylase/C17-20 lyase gene, elevating its expression in the presence of T3. TRalpha also indirectly regulated the expression of steroidogenic enzyme genes, such as steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase, by modulating the transactivation of Nur77 on steroidogenic enzyme gene promoters through protein-protein interaction. TRalpha enhanced Nur77 transactivation by excluding histone deacetylases from Nur77 in the absence of T3, whereas liganded TRalpha inhibited Nur77 transactivation, likely due to interfering with the recruitment of coactivator such as the steroid receptor coactivator-1 to Nur77. Together, these findings suggest a role of TRalpha/T3 in testicular steroidogenesis and may provide molecular mechanisms for the differential regulation of steroidogenic enzyme genes by thyroid hormone. |
