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.
Fowkes
Robert C
RC
Department of Endocrinology, Barts and the Royal London School of Medicine and Dentistry, West Smithfield, London EC1A 7BE, UK. rfow0187@itsa.ucsf.edu
Burrin
Jacky M
JM
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