Suppression of female-specific murine Cyp2b9 gene expression by growth or glucocorticoid hormones.
CYP2B9 is a constitutively and female-specifically expressed P450 isoform in mouse livers. Hypophysectomy-induced CYP2B9 mRNA expression in males to a level similar to that in females, while the operation did not affect females. Twice-daily injection of growth hormone (GH), which mimics the male pattern of GH secretion, significantly repressed hypophysectomy-induced mRNA expression in males. The same treatment completely suppressed expression in intact females. Treatments with synthetic glucocorticoid dexamethasone (DEX) suppressed expression of CYP2B9 mRNA in intact females, but not in GH-treated and un-treated hypophysectomized females. In primary cultured mouse hepatocytes, CYP2B9 mRNA expression was concentration-dependently suppressed by natural glucocorticoids such as hydrocortisone and corticosterone as well as by DEX. Glucocorticoid-mediated suppression was partially inhibited by RU486, a potent antiglucocorticoid. In contrast, RU486 by itself suppressed expression of CYP2B9 mRNA. These observations suggest that the sexually dimorphic expression of CYP2B9 is partly due to suppression by the masculine plasma GH profile and by glucocorticoid hormones.
Sakuma
Tsutomu
T
Department of Toxicology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. tsakuma@ms.toyama-mpu.ac.jp
Kitajima
Kaori
K
Nishiyama
Mie
M
Mashino
Misae
M
Hashita
Tadahiro
T
Nemoto
Nobuo
N
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002478:Cells, Cultured; D000072467:Cytochrome P450 Family 2; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005938:Glucocorticoids / Q000097:blood / Q000494:pharmacology*; D013006:Growth Hormone / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D007016:Hypophysectomy / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012737:Sex Factors; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D005938:Glucocorticoids; D013006:Growth Hormone; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C121503:Cyp2b9 protein, mouse; D000072467:Cytochrome P450 Family 2