The orphan nuclear receptor, steroidogenic factor-1, regulates the glycoprotein hormone alpha-subunit gene in pituitary gonadotropes

Mol Endocrinol. 1994 Jul;8(7):878-85. doi: 10.1210/mend.8.7.7527122.

Abstract

Tissue-specific expression of the glycoprotein hormone alpha-subunit gene in pituitary gonadotropes relies on a gonadotrope-specific element (GSE), which binds an approximately 54-kilodalton protein termed GSE-binding protein 1 (GSEB1). We report here that GSEB1 is the orphan nuclear receptor steroidogenic factor-1 (SF-1), which has been shown to be a primary regulator of steroidogenic enzymes in the adrenal gland and gonadal tissues. GSEB1 from alpha T3-1 pituitary gonadotrope cells and SF-1 from Y1 adrenocortical cells and R2C testicular Leydig cells display identical binding properties with both the GSE and SF-1 elements. Antiserum specific to the SF-1 DNA-binding domain abolishes the binding of both GSEB1 and SF-1 to both elements. SF-1 mRNA is found in the mouse pituitary and in the alpha T3-1 cell line but not in other pituitary cell lines, consistent with the pattern of GSEB 1-binding activity. The GSE element specifically enhances transcription in SF-1-containing cells. The discovery that an orphan nuclear receptor regulates the expression of both the gonadotropin hormones in the pituitary and the steroidogenic enzymes in the gonad provides a potential molecular mechanism for coordinate control in reproductive function, perhaps through an as yet unidentified endocrine ligand for SF-1.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Cortex / cytology
  • Adrenal Cortex / metabolism*
  • Adrenal Cortex Neoplasms / pathology
  • Animals
  • Base Sequence
  • Binding Sites
  • DNA / metabolism*
  • DNA-Binding Proteins / physiology*
  • Fushi Tarazu Transcription Factors
  • Gene Expression Regulation*
  • Glycoprotein Hormones, alpha Subunit / biosynthesis
  • Glycoprotein Hormones, alpha Subunit / genetics*
  • Homeodomain Proteins
  • Humans
  • Leydig Cell Tumor / pathology
  • Leydig Cells / cytology
  • Leydig Cells / metabolism*
  • Male
  • Mice
  • Molecular Sequence Data
  • Pituitary Gland, Anterior / cytology
  • Pituitary Gland, Anterior / metabolism*
  • Protein Binding
  • Rats
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism*
  • Regulatory Sequences, Nucleic Acid*
  • Steroidogenic Factor 1
  • Transcription Factors*
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • Fushi Tarazu Transcription Factors
  • Glycoprotein Hormones, alpha Subunit
  • Homeodomain Proteins
  • NR5A1 protein, human
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Steroidogenic Factor 1
  • Transcription Factors
  • steroidogenic factor 1, mouse
  • steroidogenic factor 1, rat
  • DNA