Transforming growth factor-ß1 signaling represses testicular steroidogenesis through cross-talk with orphan nuclear receptor Nur77.
PLoS One
; 9(8): e104812, 2014.
Article
en En
| MEDLINE
| ID: mdl-25140527
ABSTRACT
Transforming growth factor- ß1 (TGF-ß1) has been reported to inhibit luteinizing hormone (LH) mediated-steroidogenesis in testicular Leydig cells. However, the mechanism by which TGF-ß1 controls the steroidogenesis in Leydig cells is not well understood. Here, we investigated the possibility that TGF-ß1 represses steroidogenesis through cross-talk with the orphan nuclear receptor Nur77. Nur77, which is induced by LH/cAMP signaling, is one of major transcription factors that regulate the expression of steroidogenic genes in Leydig cells. TGF-ß1 signaling inhibited cAMP-induced testosterone production and the expression of steroidogenic genes such as P450c17, StAR and 3ß-HSD in mouse Leydig cells. Further, TGF-ß1/ALK5 signaling repressed cAMP-induced and Nur77-activated promoter activity of steroidogenic genes. In addition, TGF-ß1/ALK5-activated Smad3 repressed Nur77 transactivation of steroidogenic gene promoters by interfering with Nur77 binding to DNA. In primary Leydig cells isolated from Tgfbr2flox/flox Cyp17iCre mice, TGF-ß1-mediated repression of cAMP-induced steroidogenic gene expression was significantly less than that in primary Leydig cells from Tgfbr2flox/flox mice. Taken together, these results suggest that TGF-ß1/ALK5/Smad3 signaling represses the expression of steroidogenic genes via the suppression of Nur77 transactivation in testicular Leydig cells. These findings may provide a molecular mechanism involved in the TGF-ß1-mediated repression of testicular steroidogenesis.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Testículo
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Testosterona
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Transducción de Señal
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Factor de Crecimiento Transformador beta1
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Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares
Límite:
Animals
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2014
Tipo del documento:
Article