Cell
Volume 92, Issue 1, 9 January 1998, Pages 73-82
Journal home page for Cell

Article
An Orphan Nuclear Receptor Activated by Pregnanes Defines a Novel Steroid Signaling Pathway

https://doi.org/10.1016/S0092-8674(00)80900-9Get rights and content
Under an Elsevier user license
open archive

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 antiglucocorticoids. 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.

Cited by (0)