title: In vivo evidence for the crucial role of SF1 in steroid-producing cells of the testis, ovary and adrenal gland.
abstract: Adrenal and gonadal steroids are essential for life and reproduction. The orphan nuclear receptor SF1 (NR5A1) has been shown to regulate the expression of enzymes involved in steroid production in vitro. However, the in vivo role of this transcription factor in steroidogenesis has not been elucidated. In this study, we have generated steroidogenic-specific Cre-expressing mice to lineage mark and delete Sf1 in differentiated steroid-producing cells of the testis, the ovary and the adrenal gland. Our data show that SF1 is a regulator of the expression of steroidogenic genes in all three organs. In addition, Sf1 deletion leads to a radical change in cell morphology and loss of identity. Surprisingly, sexual development and reproduction in mutant animals were not compromised owing, in part, to the presence of a small proportion of SF1-positive cells. In contrast to the testis and ovary, the mutant adult adrenal gland showed a lack of Sf1-deleted cells and our studies suggest that steroidogenic adrenal cells during foetal stages require Sf1 to give rise to the adult adrenal population. This study is the first to show the in vivo requirements of SF1 in steroidogenesis and provides novel data on the cellular consequences of the loss of this protein specifically within steroid-producing cells.
authors.affiliation: Division of Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors.forename: F William
authors.initials: FW
authors.lastname: Buaas
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Gardiner
authors.forename: Sally
authors.initials: S
authors.lastname: Clayton
authors.forename: Pierre
authors.initials: P
authors.lastname: Val
authors.forename: Amanda
authors.initials: A
authors.lastname: Swain
mesh_terms: D000311:Adrenal Glands / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004622:Embryo, Mammalian; D005260:Female; D017353:Gene Deletion; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D019426:Integrases / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010053:Ovary / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D000072260:RNA Splicing Factors; D013737:Testis / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019076:Transgenes / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D012739:Gonadal Steroid Hormones; D008164:Luminescent Proteins; D000072260:RNA Splicing Factors; C491514:Sf1 protein, mouse; D014157:Transcription Factors; C054562:yellow fluorescent protein, Bacteria; D002786:Cholesterol Side-Chain Cleavage Enzyme; C045073:Cre recombinase; D019426:Integrases