Sex-associated expression of mouse hepatic and renal CYP2B enzymes by glucocorticoid hormones.
The expression of Cyp2b9 and Cyp2b10 genes was investigated in kidney, liver, and cultured hepatocytes of adult C57BL/6NCrj mice. The constitutive expression level of CYP2B mRNA in kidney was higher in female than in male mice, as it was in the liver where more CYP2B9 than CYP2B10 was expressed in the females, and more CYP2B10 was expressed in the males. After treatment with dexamethasone (Dex), induction of CYP2B10 mRNA and protein in the kidneys was far greater in male than in female mice. In contrast to Dex, phenobarbital (PB), pregnenolone-16 alpha-carbonitrile (PCN), and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) did not induce the expression of the Cyp2b gene in the kidneys of either sex. In the liver, PB, PCN, and DDT induced both CYP2B9 and CYP2B10 in both sexes to the same extent, whereas Dex induced only CYP2B10 and simultaneously suppressed CYP2B9. Dex-inducible expression of CYP2B mRNA was decreased by 11 beta-[4-dimethylamino]phenyl-17 beta-hydroxy-17-[1-propynyl]estra-4,9-dien-3-one (RU-486), in both the kidneys and liver from male mice, and in cultured hepatocytes. However, RU-486 itself induced the expression of CYP2B mRNA in female liver and cultured hepatocytes. Interestingly, RU-486 increased PB-inducible expression of these species in cultured hepatocytes. Gonadectomy increased the expression of CYP2B mRNA in untreated male liver, but suppressed Dex-induced expression in the kidneys of both sexes. These observations suggest that (a) there are multiple regulatory pathways in the expression of Cyp2b genes, one of which used by Dex is mediated via the glucocorticoid receptor, which is different from that used by PB, and (b) sex hormones play a role in the regulation of the sex-dependent expression of Cyp2b genes in the mouse.
Jarukamjorn
K
K
Department of Toxicology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Sakuma
T
T
Yamamoto
M
M
Ohara
A
A
Nemoto
N
N
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases; D065702:Cytochrome P-450 CYP2B6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004586:Electrophoresis; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012727:Sex Characteristics
D000927:Anticonvulsants; D005938:Glucocorticoids; D006727:Hormone Antagonists; D012333:RNA, Messenger; D015735:Mifepristone; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; D010634:Phenobarbital