Transforming growth factor-β1 signaling represses testicular steroidogenesis through cross-talk with orphan nuclear receptor Nur77

Eunsook Park, Chin Hee Song, Jae Il Park, Ryun Sup Ahn, Hueng Sik Choi, Che Myong Ko, Keesook Lee

Research output: Contribution to journalArticle

Abstract

Transforming growth factor-β1 (TGF-β1) has been reported to inhibit luteinizing hormone (LH) mediated-steroidogenesis in testicular Leydig cells. However, the mechanism by which TGF-β1 controls the steroidogenesis in Leydig cells is not well understood. Here, we investigated the possibility that TGF-β1 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-β1 signaling inhibited cAMP-induced testosterone production and the expression of steroidogenic genes such as P450c17, StAR and 3β-HSD in mouse Leydig cells. Further, TGF-β1/ALK5 signaling repressed cAMP-induced and Nur77-activated promoter activity of steroidogenic genes. In addition, TGF-β1/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-β1-mediated repression of cAMP-induced steroidogenic gene expression was significantly less than that in primary Leydig cells from Tgfbr2 flox/flox mice. Taken together, these results suggest that TGF-β1/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-β1-mediated repression of testicular steroidogenesis.

Original languageEnglish (US)
Article numbere104812
JournalPloS one
Volume9
Issue number8
DOIs
StatePublished - Aug 20 2014

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Nuclear Receptor Subfamily 4, Group A, Member 1
transforming growth factors
steroidogenesis
Transforming Growth Factors
Leydig cells
Leydig Cells
receptors
Genes
Gene Expression
gene expression
transcriptional activation
luteinizing hormone
Luteinizing Hormone
Transcriptional Activation
mice
promoter regions
Gene expression
testosterone
Testosterone
Transcription Factors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Transforming growth factor-β1 signaling represses testicular steroidogenesis through cross-talk with orphan nuclear receptor Nur77. / Park, Eunsook; Song, Chin Hee; Park, Jae Il; Ahn, Ryun Sup; Choi, Hueng Sik; Ko, Che Myong; Lee, Keesook.

In: PloS one, Vol. 9, No. 8, e104812, 20.08.2014.

Research output: Contribution to journalArticle

Park, Eunsook ; Song, Chin Hee ; Park, Jae Il ; Ahn, Ryun Sup ; Choi, Hueng Sik ; Ko, Che Myong ; Lee, Keesook. / Transforming growth factor-β1 signaling represses testicular steroidogenesis through cross-talk with orphan nuclear receptor Nur77. In: PloS one. 2014 ; Vol. 9, No. 8.
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