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Cell. 1994 Jun 3;77(5):651-61.

Nuclear receptor steroidogenic factor 1 regulates the müllerian inhibiting substance gene: a link to the sex determination cascade.

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Department of Obstetrics, Gynocology, and Reproductive Sciences, University of California, San Francisco 94143-0556.


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.

[Indexed for MEDLINE]

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