WT1 and DAX-1 regulate SF-1-mediated human P450arom gene expression in gonadal cells

Bilgin Gurates, Abraham Amsterdam, Mitsutoshi Tamura, Sijun Yang, Jianfeng Zhou, Zongjuan Fang, Sanober Amin, Siby Sebastian, Serdar E. Bulun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Binding activity of steroidogenic factor-1 (SF-1) to promoters of the majority of steroidogenic genes in response to gonadotropins is a critical mechanism that regulates steroidogenesis in gonads. Thus, the modulation of SF-1 action may be essential for the differential regulation of formation of sex steroids in the ovary. Aromatase P450 (P450arom) is the rate-limiting enzyme for estrogen formation. In this study, we characterize another nuclear receptor half site in the gonadal aromatase promoter which we show to be important for aromatase regulation. We also show herein that the stimulation of P450arom promoter activity by SF-1 in ovarian granulosa, testicular Sertoli and JEG-3 choriocarcinoma cells is inhibited by two transcription factors, Wilms' tumor suppressor gene (WT1) and dosage sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1 (DAX-1). Given the characterized roles of these transcription factors in gonadal development and function, modulation of SF-1 action by WT1 and DAX-1 may represent an important key mechanism in steroidogenesis.

Original languageEnglish (US)
Pages (from-to)61-75
Number of pages15
JournalMolecular and Cellular Endocrinology
Volume208
Issue number1-2
DOIs
StatePublished - Oct 31 2003

Keywords

  • Aromatase
  • CYP19 gene
  • DAX-1
  • Gonad
  • JEG-3
  • Nuclear receptor half site
  • Orphan nuclear hormone receptors
  • Ovarian granulosa cells
  • P450arom
  • SF-1
  • Sertoli cells
  • WT1
  • cAMP

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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