期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 330, 期 1-2, 页码 59-71出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2010.08.010
关键词
COUP-TFI; COUP-TFII; LH beta; Gene expression
Normal sexual development and reproductive function depend on precise temporal and quantitative expression of the pituitary gonadotropins, LH and FSH. LH beta-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 LH beta 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 LH beta 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 LH beta 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 LH beta gene expression. To our knowledge, these data are the first to demonstrate COUP-IF expression and function in pituitary gonadotropes. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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