In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the NR1I2 (nuclear Receptor subfamily 1, group I, member 2) gene.
PXR is a nuclear receptor whose primary function is to sense the presence of foreign toxic substances and in response up regulate the expression of proteins involved in the detoxification and clearance of these substances from the body. PXR belongs to the nuclear receptor superfamily, members of which are transcription factors characterized by a ligand-binding domain and a DNA-binding domain. PXR is a transcriptional regulator of the cytochrome P450 gene CYP3A4, binding to the response element of the CYP3A4 promoter as a heterodimer with the 9-cis retinoic acid receptor RXR. It is activated by a range of compounds that induce CYP3A4, including dexamethasone and rifampicin.
Ketoconazole is an example of one of the relatively few-known antagonists of the PXR. SPA70 (also known as LC-1) was recently identified and characterized as a potent and selective PXR antagonist.
^Ricketts ML, Boekschoten MV, Kreeft AJ, Hooiveld GJ, Moen CJ, Müller M, Frants RR, Kasanmoentalib S, Post SM, Princen HM, Porter JG, Katan MB, Hofker MH, Moore DD (July 2007). “The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand for the farnesoid and pregnane X receptors”. Molecular Endocrinology. 21 (7): 1603–16. doi:10.1210/me.2007-0133. PMID17456796.
^Kaur J, Sodhi RK, Madan J, Chahal SK, Kumar R (February 2018). “Forskolin convalesces memory in high fat diet-induced dementia in wistar rats-Plausible role of pregnane x receptors”. Pharmacological Reports. 70 (1): 161–171. doi:10.1016/j.pharep.2017.07.009. PMID29367103.
^Ding, X. (2004). “Induction of Drug Metabolism by Forskolin: The Role of the Pregnane X Receptor and the Protein Kinase A Signal Transduction Pathway”. Journal of Pharmacology and Experimental Therapeutics. 312 (2): 849–856. doi:10.1124/jpet.104.076331. ISSN0022-3565.
^Synold TW, Dussault I, Forman BM (May 2001). “The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux”. Nature Medicine. 7 (5): 584–90. doi:10.1038/87912. PMID11329060.
^Geick A, Eichelbaum M, Burk O (May 2001). “Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin”. The Journal of Biological Chemistry. 276 (18): 14581–7. doi:10.1074/jbc.M010173200. PMID11297522.
Watkins RE, Noble SM, Redinbo MR (January 2002). “Structural insights into the promiscuity and function of the human pregnane X receptor”. Current Opinion in Drug Discovery & Development. 5 (1): 150–8. PMID11865669.
Maruyama K, Sugano S (January 1994). “Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides”. Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). “Construction and characterization of a full length-enriched and a 5′-end-enriched cDNA library”. Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, McKee DD, Oliver BB, Willson TM, Zetterström RH, Perlmann T, Lehmann JM (January 1998). “An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway”. Cell. 92 (1): 73–82. doi:10.1016/S0092-8674(00)80900-9. PMID9489701.
Dotzlaw H, Leygue E, Watson P, Murphy LC (August 1999). “The human orphan receptor PXR messenger RNA is expressed in both normal and neoplastic breast tissue”. Clinical Cancer Research. 5 (8): 2103–7. PMID10473093.
Geick A, Eichelbaum M, Burk O (May 2001). “Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin”. The Journal of Biological Chemistry. 276 (18): 14581–7. doi:10.1074/jbc.M010173200. PMID11297522.
Watkins RE, Wisely GB, Moore LB, Collins JL, Lambert MH, Williams SP, Willson TM, Kliewer SA, Redinbo MR (June 2001). “The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity”. Science. 292 (5525): 2329–33. doi:10.1126/science.1060762. PMID11408620.
Zhang J, Kuehl P, Green ED, Touchman JW, Watkins PB, Daly A, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Wrighton SA, Hancock M, Kim RB, Strom S, Thummel K, Russell CG, Hudson JR, Schuetz EG, Boguski MS (October 2001). “The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants”. Pharmacogenetics. 11 (7): 555–72. doi:10.1097/00008571-200110000-00003. PMID11668216.
Gonzalez MM, Carlberg C (May 2002). “Cross-repression, a functional consequence of the physical interaction of non-liganded nuclear receptors and POU domain transcription factors”. The Journal of Biological Chemistry. 277 (21): 18501–9. doi:10.1074/jbc.M200205200. PMID11891224.
Takeshita A, Taguchi M, Koibuchi N, Ozawa Y (September 2002). “Putative role of the orphan nuclear receptor SXR (steroid and xenobiotic receptor) in the mechanism of CYP3A4 inhibition by xenobiotics”. The Journal of Biological Chemistry. 277 (36): 32453–8. doi:10.1074/jbc.M111245200. PMID12072427.
Fukuen S, Fukuda T, Matsuda H, Sumida A, Yamamoto I, Inaba T, Azuma J (November 2002). “Identification of the novel splicing variants for the hPXR in human livers”. Biochemical and Biophysical Research Communications. 298 (3): 433–8. doi:10.1016/S0006-291X(02)02469-5. PMID12413960.
Chang TK, Bandiera SM, Chen J (January 2003). “Constitutive androstane receptor and pregnane X receptor gene expression in human liver: interindividual variability and correlation with CYP2B6 mRNA levels”. Drug Metabolism and Disposition. 31 (1): 7–10. doi:10.1124/dmd.31.1.7. PMID12485946.