The expression of pregnane X receptor and its target gene, cytochrome P450 3A1, in perinatal mouse.
Recently, pregnane X receptor (PXR) has been described to mediate the genomic effects of several steroid hormones, such as progesterone (P), glucocorticoid (Dex), pregnenolone (Preg), and xenobiotics through the cytochrome P-450 3A gene family (CYP3A), which are monooxygenases, responsible for the oxidative metabolism of some endogenous substrates and xenobiotics. In the present study, we used a transient transfection reporter gene expression assay of COS-7 cells to demonstrate that P, Dex and Preg significantly stimulate PXR-mediated transcription at relatively high concentration comparable with that of progesterone near term pregnancy. In yeast two-hybrid protein interaction assay, PXR interacted with nuclear receptor coactivator proteins, SRC1, RIP140, and SUG1 in a ligand-dependent manner. The expression of PXR mRNA was observed in the liver, intestine, uterus, ovary and placenta. The expressions of PXR mRNA in the liver and ovary increased towards term about fifty-fold compared with that of non-pregnancy and decreased postpartum. Its expression in the placenta was not drastically changed towards term. CYP3A, a target gene of PXR, was also expressed in the liver, ovary, and placenta. The expressions of CYP3A mRNA as well as PXR in the liver and ovary increased about 20-fold during prenatal period. These data suggest that PXR may play certain roles in perinatal period, possibly in the protection of the feto-maternal system from the toxic effect of endogenous steroids and foreign substrates.
Masuyama
H
H
Department of Obstetrics and Gynecology, Okayama University Medical School, 2-5-1, Shikata, 700-8558, Okayama, Japan. masuyama@cc.okayama-u.ac.jp
Hiramatsu
Y
Y
Mizutani
Y
Y
Inoshita
H
H
Kudo
T
T
D000818:Animals; D019556:COS Cells; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011247:Pregnancy; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D011987:Receptors, Steroid / Q000235:genetics*; D013256:Steroids / Q000494:pharmacology; D014018:Tissue Distribution; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D013256:Steroids; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A