Steroidogenic factor 1 and Dax-1 colocalize in multiple cell lineages: potential links in endocrine development.

Journal Article (Journal Article)

Mutations of the orphan nuclear receptors, steroidogenic factor 1 (SF-1) and DAX-1, cause complex endocrine phenotypes that include impaired adrenal development and hypogonadotrophic hypogonadism. These similar phenotypes suggest that SF-1 and DAX-1 act in the same pathway(s) of endocrine development. To explore this model, we now compare directly their sites of expression. In mouse embryos, SF-1 expression in the urogenital ridge and brain either preceded or coincided with Dax-1 expression, with coordinate expression thereafter in the adrenal cortex, testis, ovary, hypothalamus, and anterior pituitary. The striking colocalization of SF-1 and Dax-1 supports the model that they are intimately linked in a common pathway of endocrine development. The slightly earlier onset of SF-1 expression and its ability to bind specifically to a conserved sequence in the Dax-1 5'-flanking region suggested that SF-1 may activate Dax-1 expression. However, promoter activity of Dax-1 5'-flanking sequences did not require this potential SF-1-responsive element, and Dax-1 expression was unimpaired in knockout mice lacking SF-1, establishing that SF-1 is not required for Dax-1 gene expression in these settings. Although the precise mechanisms remain to be established and may be multifactorial, our results strongly suggest that these two orphan nuclear receptors interact in a common pathway of endocrine development.

Full Text

Duke Authors

Cited Authors

  • Ikeda, Y; Swain, A; Weber, TJ; Hentges, KE; Zanaria, E; Lalli, E; Tamai, KT; Sassone-Corsi, P; Lovell-Badge, R; Camerino, G; Parker, KL

Published Date

  • October 1996

Published In

Volume / Issue

  • 10 / 10

Start / End Page

  • 1261 - 1272

PubMed ID

  • 9121493

International Standard Serial Number (ISSN)

  • 0888-8809

Digital Object Identifier (DOI)

  • 10.1210/mend.10.10.9121493


  • eng

Conference Location

  • United States