Article ID Journal Published Year Pages File Type
2196681 Molecular and Cellular Endocrinology 2010 13 Pages PDF
Abstract

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.

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