Involvement of cyclic adenosine 5'-monophosphate response element-binding protein, steroidogenic factor 1, and Dax-1 in the regulation of gonadotropin-inducible ovarian transcription factor 1 gene expression by follicle-stimulating hormone in ovarian granulosa cells

Endocrinology. 2003 May;144(5):1920-30. doi: 10.1210/en.2002-221070.


Upon FSH stimulation, many genes are acutely induced in granulosa cells. Gonadotropin-inducible ovarian transcription factor 1 (GIOT1) represents a novel member of the group of transcriptional repressors that belong to one such gene. To investigate the mechanism of this transcriptional activation, a rat GIOT1 promoter region was isolated and subsequently ligated to a luciferase vector and transfected to freshly prepared granulosa cells. A luciferase reporter gene driven by 0.8 kb of the GIOT1 5'-flanking region was highly expressed in response to FSH. Deletion and mutational analyses indicated that two response elements, including a steroidogenic factor 1 (SF-1) site and a cAMP response element (CRE), are required for the activation of the gene by FSH. Gel shift experiments also indicated that SF-1 and CRE binding protein specifically bind to each site. To reveal the relationship between SF-1 and the cAMP-dependent protein kinase A pathway, cotransfection was performed using SF-1-deficient cells. Although SF-1 and the catalytic subunit of protein kinase A individually caused a modest stimulation of the GIOT1 promoter, dramatic synergistic effects were observed in the case of cotransfection. Although the amount of SF-1 remained unchanged in response to FSH in granulosa cells, Dax-1 expression immediately decreased. The ectopic expression of Dax-1 inhibited the SF-1-dependent GIOT1 promoter activity. These results suggest that the synergistic action of CRE binding protein and SF-1 and the rapid down-regulation of Dax-1 are responsible for the acute induction of GIOT1 gene by gonadotropin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence / genetics
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / physiology*
  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins / physiology*
  • Down-Regulation
  • Female
  • Follicle Stimulating Hormone / pharmacology*
  • Fushi Tarazu Transcription Factors
  • Gene Expression / drug effects
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism*
  • Homeodomain Proteins
  • Molecular Sequence Data
  • Rats
  • Rats, Wistar
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid / physiology*
  • Repressor Proteins*
  • Steroidogenic Factor 1
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology*


  • Cyclic AMP Response Element-Binding Protein
  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins
  • Fushi Tarazu Transcription Factors
  • Giot1 protein, rat
  • Homeodomain Proteins
  • Nr0b1 protein, rat
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • Steroidogenic Factor 1
  • Transcription Factors
  • steroidogenic factor 1, rat
  • Follicle Stimulating Hormone