The orphan nuclear receptors COUP-TFI and COUP-TFII regulate expression of the gonadotropin LHβ gene

Mol Cell Endocrinol. 2010 Dec 15;330(1-2):59-71. doi: 10.1016/j.mce.2010.08.010. Epub 2010 Aug 24.


Normal sexual development and reproductive function depend on precise temporal and quantitative expression of the pituitary gonadotropins, LH and FSH. LHβ-subunit gene expression is achieved by transcription factors acting at highly conserved and closely spaced cis-elements in the proximal 200 base pairs of the promoter. We now demonstrate that LHβ promoter activity is further regulated by the orphan nuclear receptors, chicken ovalbumin upstream promoter-transcription factors (COUP-TFI and COUP-TFII). These data establish that COUP-TFs are expressed in primary pituitary gonadotropes and two gonadotrope-derived cell lines. COUP-TFs bind to two promoter regions in the LHβ gene which overlap but are distinct from two previously defined cis-elements for another orphan nuclear receptor, steroidogenic factor-1 (SF-1). Transient transfection studies demonstrated that COUP-TFs stimulate LHβ gene promoter activity in the absence of SF-1, but blunt SF-1-mediated stimulation of gene expression in a reporter construct containing both SF-1 cis-elements (GSEs). Evaluation of constructs containing mutations or truncations in the GSEs revealed a complex pattern of activation and inhibition by COUP-TF on this promoter, suggesting multiple mechanisms by which this factor modulates LHβ gene expression. To our knowledge, these data are the first to demonstrate COUP-TF expression and function in pituitary gonadotropes.

MeSH terms

  • Animals
  • Base Sequence
  • Binding, Competitive
  • COUP Transcription Factor I / metabolism*
  • COUP Transcription Factor II / metabolism*
  • Cell Line
  • Chickens
  • Chromatin Immunoprecipitation
  • DNA / metabolism
  • Gene Expression Regulation*
  • Gonadotrophs / metabolism
  • Humans
  • Luteinizing Hormone, beta Subunit / genetics*
  • Luteinizing Hormone, beta Subunit / metabolism
  • Mice
  • Molecular Sequence Data
  • Mutation / genetics
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Protein Transport
  • RNA, Small Interfering / metabolism
  • Rats
  • Receptors, LHRH / genetics
  • Steroidogenic Factor 1 / metabolism


  • COUP Transcription Factor I
  • COUP Transcription Factor II
  • Luteinizing Hormone, beta Subunit
  • Protein Subunits
  • RNA, Small Interfering
  • Receptors, LHRH
  • Steroidogenic Factor 1
  • DNA