Collaborated regulation of female-specific murine Cyp3a41 gene expression by growth and glucocorticoid hormones

Tsutomu Sakuma; Kaori Kitajima; Mie Nishiyama; Yusuke Endo; Kimiko Miyauchi; Kanokwan Jarukamjorn; Nobuo Nemoto

doi:10.1016/j.bbrc.2003.12.114

Collaborated regulation of female-specific murine Cyp3a41 gene expression by growth and glucocorticoid hormones

Biochem Biophys Res Commun. 2004 Feb 6;314(2):495-500. doi: 10.1016/j.bbrc.2003.12.114.

Authors

Tsutomu Sakuma¹, Kaori Kitajima, Mie Nishiyama, Yusuke Endo, Kimiko Miyauchi, Kanokwan Jarukamjorn, Nobuo Nemoto

Affiliation

¹ Department of Toxicology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, 930-0194 Toyama, Japan. tsakuma@ms.toyama-mpu.ac.jp

PMID: 14733933
DOI: 10.1016/j.bbrc.2003.12.114

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenal Glands / metabolism
Animals
Aryl Hydrocarbon Hydroxylases / genetics
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System / biosynthesis*
Cytochrome P-450 Enzyme System / genetics*
Dexamethasone / metabolism*
Dose-Response Relationship, Drug
Female
Gene Expression Regulation*
Glucocorticoids / metabolism*
Growth Hormone / metabolism
Hepatocytes / metabolism
Hormone Antagonists / pharmacology
Liver / metabolism
Membrane Proteins
Mice
Mice, Inbred C57BL
Mifepristone / pharmacology
Oxidoreductases / biosynthesis*
Oxidoreductases / genetics*
Oxidoreductases, N-Demethylating / genetics
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sex Factors
Time Factors
Tyrosine Transaminase / metabolism

Substances

Glucocorticoids
Hormone Antagonists
Membrane Proteins
RNA, Messenger
Mifepristone
Dexamethasone
Growth Hormone
Cytochrome P-450 Enzyme System
Cyp3a41a protein, mouse
Oxidoreductases
Aryl Hydrocarbon Hydroxylases
Cyp3a11 protein, mouse
Cytochrome P-450 CYP3A
Oxidoreductases, N-Demethylating
Tyrosine Transaminase