Collaborated regulation of female-specific murine Cyp3a41 gene expression by growth and glucocorticoid hormones.
CYP3A41 is a female-specific major CYP3A in mouse livers. Adrenalectomy decreased expression of CYP3A41 as well as CYP3A11, another major CYP3A, and dexamethasone (DEX) restored the decreased expression. Hypophysectomy completely abolished CYP3A41 expression and growth hormone (GH) replacement only slightly restored the expression. Treatment with DEX alone did not induce expression of either CYP3A41 or CYP3A11 in hypophysectomized mice. However, combined treatment with GH and DEX strongly induced expression of CYP3A41 but not CYP3A11. In primary cultured mouse hepatocytes, DEX induced expression of both CYP3A41 and CYP3A11, and DEX-inducible expression of CYP3A41 was suppressed by RU486, a potent antiglucocorticoid. In contrast, RU486 by itself enhanced basal expression of CYP3A11 mRNA, while it showed no inhibitory effect on DEX-inducible expression. These observations indicate that glucocorticoids may participate in the GH-dependent control of the Cyp3a41 gene expression, probably mediated via the glucocorticoid receptor, which may be different from that of the Cyp3a11 gene expression.
Sakuma
Tsutomu
T
Department of Toxicology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, 930-0194 Toyama, Japan. tsakuma@ms.toyama-mpu.ac.jp
Kitajima
Kaori
K
Nishiyama
Mie
M
Endo
Yusuke
Y
Miyauchi
Kimiko
K
Jarukamjorn
Kanokwan
K
Nemoto
Nobuo
N
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics*; D003907:Dexamethasone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics*; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013997:Time Factors; D014444:Tyrosine Transaminase / Q000378:metabolism
D005938:Glucocorticoids; D006727:Hormone Antagonists; D008565:Membrane Proteins; D012333:RNA, Messenger; D015735:Mifepristone; D003907:Dexamethasone; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; C408695:Cyp3a41a protein, mouse; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; C496508:Cyp3a11 protein, mouse; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D014444:Tyrosine Transaminase