Abstract
Products of steroidogenic factor 1 (SF-1) and Wilms' tumor 1 (WT1) genes are essential for mammalian gonadogenesis prior to sexual differentiation. In males, SF-1 participates in sexual development by regulating expression of the polypeptide hormone Müllerian inhibiting substance (MIS). Here, we show that WT1 -KTS isoforms associate and synergize with SF-1 to promote MIS expression. In contrast, WT1 missense mutations, associated with male pseudohermaphroditism in Denys-Drash syndrome, fail to synergize with SF-1. Additionally, the X-linked, candidate dosage-sensitive sex-reversal gene, Dax-1, antagonizes synergy between SF-1 and WT1, most likely through a direct interaction with SF-1. We propose that WT1 and Dax-1 functionally oppose each other in testis development by modulating SF-1-mediated transactivation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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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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Cell Line
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DAX-1 Orphan Nuclear Receptor
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DNA / metabolism
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DNA-Binding Proteins / analysis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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Disorders of Sex Development / genetics
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Female
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Fushi Tarazu Transcription Factors
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Gene Expression Regulation, Developmental / genetics
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Genes, Wilms Tumor / physiology
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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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Models, Genetic
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Mutation
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Organ Specificity
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Ovary / chemistry
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Ovary / embryology
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Placenta / cytology
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RNA, Messenger / analysis
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Rats
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / metabolism
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Receptors, Retinoic Acid / physiology*
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Repressor Proteins*
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Sex Determination Processes
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Steroidogenic Factor 1
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Testicular Hormones / genetics*
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Testis / chemistry
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Testis / embryology
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Transcription Factors / analysis
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Transcriptional Activation / genetics*
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WT1 Proteins
Substances
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DAX-1 Orphan Nuclear Receptor
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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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NR0B1 protein, human
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NR5A1 protein, human
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Nr0b1 protein, rat
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid
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Repressor Proteins
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Steroidogenic Factor 1
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Testicular Hormones
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Transcription Factors
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WT1 Proteins
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steroidogenic factor 1, rat
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Anti-Mullerian Hormone
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DNA