ERα/E2 signaling suppresses the expression of steroidogenic enzyme genes via cross-talk with orphan nuclear receptor Nur77 in the testes

Seung Yon Lee, Eunsook Park, Seung Chang Kim, Ryun Sup Ahn, CheMyong Ko, Keesook Lee

Research output: Contribution to journalArticle

Abstract

Estrogen receptor alpha (ERα) has been reported to affect steroidogenesis in testicular Leydig cells, but its molecular mechanism remains unclear. Here, we investigate the effect of estrogen and ERα on Nur77, a major transcription factor that regulates the expression of steroidogenic enzyme genes. In MA-10 Leydig cells, estradiol (E2) treatment, and interestingly ERα overexpression, suppressed the cAMP-induced and Nur77-activated promoter activity of steroidogenic enzyme genes via the suppression of Nur77 transactivation. ERα physically interacted with Nur77 and inhibited its DNA binding activity. In addition, ERα/E2 signaling decreased Nur77 protein levels. Consistent with the above results, the testicular testosterone level was higher in Leydig cell-specific ERα knock-out mice (ERαflox/floxCyp17iCre) than in wild-type mice (ERαflox/flox). Taken together, these results suggest that ERα/E2 signaling controls the Nur77-mediated expression of steroidogenic enzyme genes in Leydig cells. These findings may provide a mechanistic explanation for the local regulation of testicular steroidogenesis by estrogenic compounds and ERα.

Original languageEnglish (US)
Pages (from-to)91-103
Number of pages13
JournalMolecular and Cellular Endocrinology
Volume362
Issue number1-2
DOIs
StatePublished - Oct 15 2012

Fingerprint

Nuclear Receptor Subfamily 4, Group A, Member 1
Estrogen Receptor alpha
Testis
Genes
Leydig Cells
Enzymes
Estrogens
Knockout Mice
Transcriptional Activation
Testosterone
Estradiol
Transcription Factors

Keywords

  • Estrogen
  • Estrogen receptor alpha
  • Leydig cell
  • Nur77
  • Steroidogenesis
  • Testis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

ERα/E2 signaling suppresses the expression of steroidogenic enzyme genes via cross-talk with orphan nuclear receptor Nur77 in the testes. / Lee, Seung Yon; Park, Eunsook; Kim, Seung Chang; Ahn, Ryun Sup; Ko, CheMyong; Lee, Keesook.

In: Molecular and Cellular Endocrinology, Vol. 362, No. 1-2, 15.10.2012, p. 91-103.

Research output: Contribution to journalArticle

Lee, Seung Yon ; Park, Eunsook ; Kim, Seung Chang ; Ahn, Ryun Sup ; Ko, CheMyong ; Lee, Keesook. / ERα/E2 signaling suppresses the expression of steroidogenic enzyme genes via cross-talk with orphan nuclear receptor Nur77 in the testes. In: Molecular and Cellular Endocrinology. 2012 ; Vol. 362, No. 1-2. pp. 91-103.
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