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

First Author  Kliewer SA Year  1998
Journal  Cell Volume  92
Issue  1 Pages  73-82
PubMed ID  9489701 Mgi Jnum  J:51034
Mgi Id  MGI:1314507 Doi  10.1016/s0092-8674(00)80900-9
Citation  Kliewer SA, et al. (1998) An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 92(1):73-82
abstractText  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 16alpha-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.
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