The nuclear receptor SF-1 mediates sexually dimorphic expression of Mullerian Inhibiting Substance, in vivo.
Mullerian Inhibiting Substance (MIS) functions to promote regression of the Mullerian duct during male development. Maintaining the sexually dimorphic pattern of MIS expression is essential for proper mammalian reproductive tract development. Here, we show that the intricate spatial and temporal pattern of MIS expression is directed by a remarkably small proximal promoter of only 180 base pairs in length. Expression of the MIS-human growth hormone transgene (MIS/GH) is restricted to Sertoli cells in embryonic testis and to granulosa cells of postnatal ovary, consistent with the known MIS expression pattern. The proximal MIS promoter is therefore sufficient to direct the initiation and the maintenance of MIS gene expression in both sexes. Moreover, in vivo MIS promoter activity requires an intact binding site for the orphan nuclear receptor SF-1. Taken together, these data strongly suggest that SF-1 directly activates MIS in embryonic and postnatal gonads. Consistent with the proposed role of SF-1 in mammalian sex-determination, our study provides physiological evidence that a SF-1 binding site is essential for gene activation of an embryonic testis-specific marker.
Giuili
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G
Department of Physiology, University of California, San Francisco, 94143-0444, USA.
Shen
W H
WH
Ingraham
H A
HA
D000818:Animals; D054304:Anti-Mullerian Hormone; D002467:Cell Nucleus / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins; D006107:Granulosa Cells / Q000502:physiology*; D006131:Growth Inhibitors / Q000096:biosynthesis*; D018398:Homeodomain Proteins; D019382:Human Growth Hormone / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins; D009928:Organ Specificity; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012708:Sertoli Cells / Q000378:metabolism*; D012727:Sex Characteristics; D051876:Sex-Determining Region Y Protein; D054339:Steroidogenic Factor 1; D013735:Testicular Hormones / Q000096:biosynthesis*; D013737:Testis / Q000196:embryology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology*; D015533:Transcriptional Activation
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D006023:Glycoproteins; D006131:Growth Inhibitors; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D051876:Sex-Determining Region Y Protein; D054339:Steroidogenic Factor 1; D013735:Testicular Hormones; D014157:Transcription Factors; D019382:Human Growth Hormone; D054304:Anti-Mullerian Hormone