The orphan nuclear receptor, steroidogenic factor-1, regulates the glycoprotein hormone alpha-subunit gene in pituitary gonadotropes.
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.
Barnhart
K M
KM
Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093-0674.
Mellon
P L
PL
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000502:physiology*; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation; D015292:Glycoprotein Hormones, alpha Subunit / Q000096:biosynthesis / Q000235:genetics*; D018398:Homeodomain Proteins; D006801:Humans; D007984:Leydig Cell Tumor / Q000473:pathology; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D015292:Glycoprotein Hormones, alpha Subunit; D018398:Homeodomain Proteins; C515057:NR5A1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; C515060:steroidogenic factor 1, rat; D004247:DNA