Nuclear receptor steroidogenic factor 1 regulates the müllerian inhibiting substance gene: a link to the sex determination cascade.
Normal male sex differentiation requires that Sertoli cells in the embryonic testes produce müllerian inhibiting substance (MIS), a TGF beta-like hormone that causes müllerian duct regression. In primary Sertoli cells, the orphan nuclear receptor, steroidogenic factor 1 (SF-1), regulates the MIS gene by binding to a conserved upstream regulatory element. In heterologous (HeLa) cells, MIS gene activation by SF-1 requires removal of the SF-1 ligand-binding domain, implicating a Sertoli cell-specific ligand or cofactor. Finally, the sexually dimorphic expression of SF-1 during development coincides with MIS expression and müllerian duct regression. We propose that SF-1 regulates MIS in vivo and participates directly in the process of mammalian sex determination.
Shen
W H
WH
Department of Obstetrics, Gynocology, and Reproductive Sciences, University of California, San Francisco 94143-0556.
Moore
C C
CC
Ikeda
Y
Y
Parker
K L
KL
Ingraham
H A
HA
D000818:Animals; D054304:Anti-Mullerian Hormone; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000235:genetics*; D018398:Homeodomain Proteins; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009095:Mullerian Ducts / Q000196:embryology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012708:Sertoli Cells / Q000378:metabolism; D012727:Sex Characteristics; D012733:Sex Differentiation / Q000235:genetics* / Q000502:physiology*; D054339:Steroidogenic Factor 1; D013735:Testicular Hormones / Q000235:genetics*; D013737:Testis / Q000196:embryology; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D006023:Glycoproteins; D006131:Growth Inhibitors; D018398:Homeodomain Proteins; C515057:NR5A1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D013735:Testicular Hormones; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; C515060:steroidogenic factor 1, rat; D054304:Anti-Mullerian Hormone; D004247:DNA