THE ORPHAN NUCLEAR RECEPTOR, STEROIDOGENIC FACTOR-I, REGULATES THE GLYCOPROTEIN HORMONE ALPHA-SUBUNIT GENE IN PITUITARY GONADOTROPES

Tissue-specific expression of the glycoprotein hormone cu-subunit gene in pituitary gonadotropes relies on a gonadotrope-specific element (G SE), which binds an approximately 54-kilodalton protein termed GSE-bin ding protein 1 (GSEB1). We report here that GSEB1 is the orphan nuclea r receptor steroidogenic factor-1 (SF-1), which has been shown to be a primary regulator of steroidogenic enzymes in the adrenal gland and g onadal tissues. GSEB1 from alpha T3-1 pituitary gonadotrope cells and SF-1 from Y1 adrenocortical cells and R2C testicular Leydig cells disp lay identical binding properties with both the GSE and SF-1 elements. Antiserum specific to the SF-1 DNA-binding domain abolishes the bindin g of both GSEB1 and SF-1 to both elements. SF-1 mRNA is found in the m ouse pituitary and in the alpha T3-1 cell line but not in other pituit ary cell lines, consistent with the pattern of GSEB1-binding activity. The GSE element specifically enhances transcription in SF-1-containin g cells. The discovery that an orphan nuclear receptor regulates the e xpression of both the gonadotropin hormones in the pituitary and the s teroidogenic enzymes in the gonad provides a potential molecular mecha nism for coordinate control in reproductive function, perhaps through an as yet unidentified endocrine ligand for SF-1.