Sex-associated expression of mouse hepatic and renal CYP2B enzymes by glucocorticoid hormones

Citation
K. Jarukamjorn et al., Sex-associated expression of mouse hepatic and renal CYP2B enzymes by glucocorticoid hormones, BIOCH PHARM, 62(2), 2001, pp. 161-169
Citations number
58
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
62
Issue
2
Year of publication
2001
Pages
161 - 169
Database
ISI
SICI code
0006-2952(20010715)62:2<161:SEOMHA>2.0.ZU;2-K
Abstract
The expression of Cyp2b9 and Cyp2b10 genes was investigated in kidney, live r, and cultured hepatocytes of adult C57BL/6NCrj mice. The constitutive exp ression level of CYP2B mRNA in kidney was higher in female than in male mic e, as it was in the liver where moro CYP2B9 than CYP2B10 was expressed in t he females, and more CYP2B10 was expressed in the males. After treatment wi th dexamethasone (Dex), induction of CYP2B10 mRNA and protein in the kidney s was far greater in male than in female mice. In contrast to Dex, phenobar bital (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 Cy p2b gene in the kidneys of either sex. In the liver, PB, PCN, and DDT induc ed both CYP2B9 and CYP2B10 in both sexes to the same extent, whereas Dex in duced only CYP2B10 and simultaneously suppressed CYP2B9. Dex-inducible expr ession of CYP2B mRNA was decreased by 11 beta-[4-dimethylamino]phenyl-17 be ta -hydroxy-17-[1-propynyl]estra-4,9-dien-3-one (RU-486), in both the kidne ys and liver from male mice, and in cultured hepatocytes. However, RU-486 i tself induced the expression of CYP2B mRNA in female liver and cultured hep atocytes. interestingly, RU-486 increased PB-inducible expression of these species in cultured hepatocytes. Gonadectomy increased the expression of CY P2B mRNA in untreated male liver, but suppressed Dex-induced expression in the kidneys of both sexes. These observations suggest that (a) there are mu ltiple regulatory pathways in the expression of Cyp2b genes, one of which u sed 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. (C) 2001 Elsevie r Science Inc. All rights reserved.