An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway

Steven A. Kliewer, John T. Moore, Laura Wade, Jeff L. Staudinger, Michael A. Watson, Stacey A. Jones, David D. McKee, Beverly B. Oliver, Timothy M. Willson, Rolf H. Zetterström, Thomas Perlmann, Jürgen M. Lehmann

Research output: Contribution to journalArticle

1231 Scopus citations

Abstract

Steroid hormones exert profound effects on differentiation, development, and homeostasis in higher eukaryotes through interactions with nuclear receptors. We describe a novel orphan nuclear receptor, termed the pregnane X receptor (PXR), that is activated by naturally occurring steroids such as pregnenolone and progesterone, and synthetic glucocorticoids and anti- glucocorticoids. PXR exists as two isoforms, PXR.1 and PXR.2, that are differentially activated by steroids. Notably, PXR.1 is efficaciously activated by pregnenolone 16α-carbonitrile, a glucocorticoid receptor antagonist that induces the expression of the CYP3A family of steroid hydroxylases and modulates sterol and bile acid biosynthesis in vivo. Our results provide evidence for the existence of a novel steroid hormone signaling pathway with potential implications in the regulation of steroid hormone and sterol homeostasis.

Original languageEnglish (US)
Pages (from-to)73-82
Number of pages10
JournalCell
Volume92
Issue number1
DOIs
StatePublished - Jan 9 1998

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kliewer, S. A., Moore, J. T., Wade, L., Staudinger, J. L., Watson, M. A., Jones, S. A., McKee, D. D., Oliver, B. B., Willson, T. M., Zetterström, R. H., Perlmann, T., & Lehmann, J. M. (1998). An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell, 92(1), 73-82. https://doi.org/10.1016/S0092-8674(00)80900-9