Regulation of Mouse Hepatic CYP2D9 mRNA Expression by Growth and Adrenal Hormones

The constitutive expression of CYP2D9 is sexually dimorphic, namely, strong in males, but diminutive in females. Repetition of mimic growth hormone (GH) secretion pattern impressively returned the mRNA expression level to that in intact mice: the GH secretion pattern’s regulation of CYP2D9 mRNA expr...

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Bibliographic Details
Published in:DRUG METABOLISM AND PHARMACOKINETICS 2006-01, Vol.21 (1), p.29-36
Main Authors: Jarukamjorn, Kanokwan, Sakuma, Tsutomu, Jaruchotikamol, Atika, Oguro, Miki, Nemoto, Nobuo
Format: Article
Language:English
Subjects:
Adrenal Cortex Hormones - pharmacology
Adrenalectomy
Animals
Animals, Newborn
CYP2D9
Cytochrome P-450 Enzyme System - biosynthesis
Cytochrome P-450 Enzyme System - genetics
Cytochrome P450 Family 2
dexamethasone
Dexamethasone - pharmacology
Female
growth hormone
Growth Hormone - pharmacology
Male
Mice
Mice, Inbred C57BL
monosodium glutamate
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Sex Characteristics
Sodium Glutamate - pharmacology
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Summary:The constitutive expression of CYP2D9 is sexually dimorphic, namely, strong in males, but diminutive in females. Repetition of mimic growth hormone (GH) secretion pattern impressively returned the mRNA expression level to that in intact mice: the GH secretion pattern’s regulation of CYP2D9 mRNA expression has been predominantly disrupted by exogenous GH-administration. The extensive decline of CYP2D9 mRNA expression becoming a sexually non-specific P450 in 9-week-old male mice exposed as neonates to monosodium L-glutamate (MSG) suggested that the male GH secretion pattern is a key to the regulation of male-specific CYP2D9 mRNA expression in adult mice. Dexamethasone (Dex) showed possibility to induce CYP2D9 mRNA expression in adult MSG-neonatally treated mice of either sex. However, the antagonism was observed by co-administration of Dex and GH in the males. Dex-administration in adrenalectomized mice significantly elevated CYP2D9 mRNA expression levels. These findings suggest that an adrenal hormone participates in the regulatory mechanism of CYP2D9 mRNA expression in association with GH.
ISSN:1347-4367
1880-0920
DOI:10.2133/dmpk.21.29