Steroidogenic factor-1 enhances basal and forskolin-stimulated transcription of the human glycoprotein hormone alpha-subunit gene in GH3 cells.
Steroidogenic factor-1 (SF-1) is a key regulator of endocrine development, and mediates expression of gonadotrophin-specific genes in the pituitary. Basal and hormone stimulated transcription of the human glycoprotein hormone alpha-subunit gene (alphaGSU) in gonadotrophs involves SF-1 and its cognate binding site, the gonadotroph-specific element (GSE). In this study, we demonstrate that SF-1 significantly enhances basal and forskolin-stimulated transcription of the human alphaGSU promoter in GH(3) cells. Mutation of the GSE abolished the SF-1-mediated transactivation of basal alphaGSU promoter activity, and significantly attenuated the forskolin effect by 50%. Mutation of the Ser203 residue in SF-1 to Ala blocked basal transactivation of alphaGSU promoter activity, and halved the forskolin effect. These data collectively reveal a direct role for SF-1 and the GSE in mediating basal and forskolin-stimulated transcription of the human alphaGSU promoter in GH(3) cells. The phosphorylation site at Ser203 appears to be required for these effects.
Department of Endocrinology, Barts and the Royal London School of Medicine and Dentistry, West Smithfield, London EC1A 7BE, UK. rfow0187@itsa.ucsf.edu
Robert C
RC
Fowkes
Jacky M
JM
Burrin
D000704:Analysis of Variance; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology*; D051717:Fushi Tarazu Transcription Factors; D015870:Gene Expression; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics*; D013006:Growth Hormone / Q000378:metabolism; D018398:Homeodomain Proteins; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology*; D014158:Transcription, Genetic
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; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D005576:Colforsin; D011388:Prolactin; D013006:Growth Hormone