Action of hormone responsive sequence in 2.3 kb promoter of CYP11A1

Mol Cell Endocrinol. 2001 Apr 25;175(1-2):205-10. doi: 10.1016/s0303-7207(01)00388-4.

Abstract

The CYP11A1 gene encodes cytochrome P450scc, the enzyme catalyzing the first step of steroid biosynthesis in the adrenal and gonad. We generated transgenic mice containing 2.3 kb of the 5'-flanking region of CYP11A1 driving LacZ reporter gene expression, in order to study hormonal control of CYP11A1 gene expression in different tissues. This 2.3 kb fragment contains information for hormonal control; by ACTH and hCG which increased reporter gene expression, in the adrenal and testis of transgenic mice respectively, while dexamethasone administration decreased reporter activity in the adrenal. The 5'-fragment of CYP11A1 has appreciable promoter activities in mouse adrenal Y1 cells but not in non-steroidogenic COS-1 cells, showing cell-type specificity. Transcription factor SF-1 activates the 2.3 kb promoter, which can be potentiated by cotransfection with c-Jun in steroidogenic JEG3 cells but not in COS-1 cells. We conclude that the 2.3 kb region of CYP11A1 contains elements controlling hormonal-dependent, cell-type-specific expression. In addition, c-Jun and SF-1 could act synergistically to activate CYP11A1 gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / cytology
  • Adrenocorticotropic Hormone / pharmacology
  • Animals
  • Base Sequence / drug effects
  • Base Sequence / genetics
  • Cholesterol Side-Chain Cleavage Enzyme / genetics*
  • Chorionic Gonadotropin / pharmacology
  • DNA-Binding Proteins / pharmacology
  • Dexamethasone / pharmacology
  • Drug Synergism
  • Female
  • Fushi Tarazu Transcription Factors
  • Homeodomain Proteins
  • Hormones / pharmacology*
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Organ Specificity
  • Promoter Regions, Genetic / drug effects*
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins c-jun / pharmacology
  • Receptors, Cytoplasmic and Nuclear
  • Steroidogenic Factor 1
  • Testis / cytology
  • Transcription Factors / pharmacology
  • Tumor Cells, Cultured

Substances

  • Chorionic Gonadotropin
  • DNA-Binding Proteins
  • Fushi Tarazu Transcription Factors
  • Homeodomain Proteins
  • Hormones
  • Proto-Oncogene Proteins c-jun
  • Receptors, Cytoplasmic and Nuclear
  • Steroidogenic Factor 1
  • Transcription Factors
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Cholesterol Side-Chain Cleavage Enzyme