Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anti-Mullerian Hormone
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Base Sequence
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Binding Sites
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Cell Nucleus / metabolism
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DNA / genetics
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DNA-Binding Proteins / metabolism*
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Female
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Fushi Tarazu Transcription Factors
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Gene Expression Regulation
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Glycoproteins*
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Growth Inhibitors / genetics*
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Homeodomain Proteins
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Humans
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Male
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Mice
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Molecular Sequence Data
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Mullerian Ducts / embryology
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Mullerian Ducts / metabolism
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Promoter Regions, Genetic
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Rats
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Rats, Sprague-Dawley
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Sertoli Cells / metabolism
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Sex Characteristics
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Sex Differentiation / genetics*
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Sex Differentiation / physiology*
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Steroidogenic Factor 1
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Testicular Hormones / genetics*
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Testis / embryology
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Transcription Factors / metabolism*
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Transcriptional Activation
Substances
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DNA-Binding Proteins
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Fushi Tarazu Transcription Factors
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Glycoproteins
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Growth Inhibitors
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Homeodomain Proteins
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NR5A1 protein, human
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Receptors, Cytoplasmic and Nuclear
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Steroidogenic Factor 1
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Testicular Hormones
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Transcription Factors
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steroidogenic factor 1, mouse
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steroidogenic factor 1, rat
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Anti-Mullerian Hormone
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DNA