Document Detail

Growth hormone regulation and developmental expression of rat hepatic CYP3A18, CYP3A9, and CYP3A2.
MedLine Citation:
PMID:  10736428     Owner:  NLM     Status:  MEDLINE    
The present study investigated the role of growth hormone (GH) in hepatic CYP3A18 and CYP3A9 expression in prepubertal and adult male rats. For comparison, the effects of GH on CYP3A2 expression were also measured. Initial experiments demonstrated that CYP3A18 mRNA levels were greater during puberty and adulthood than during the prepubertal period, CYP3A9 mRNA was not expressed until puberty and its expression increased in adulthood, and CYP3A2 mRNA levels were relatively constant from prepuberty to adult life. Hypophysectomy, which results in the loss of multiple pituitary factors including GH, increased CYP3A2 and CYP3A18 mRNA expression 3- to 4-fold, but it did not affect CYP3A9 mRNA levels or CYP3A-mediated testosterone 2beta- or 6beta-hydroxylase activity in adult rats. GH administered as twice daily s.c. injections (0.12 microg/g body weight) to hypophysectomized or intact adult rats did not affect CYP3A18 or CYP3A9 mRNA expression. The same treatment decreased CYP3A2 mRNA and protein and testosterone 2beta- and 6beta-hydroxylase activity levels in intact but not hypophysectomized rats. However, in intact prepubertal rats, intermittent GH administration decreased CYP3A18 and CYP3A2 mRNA levels, but a higher dosage (3.6 microg/g) was required to suppress CYP3A2. Overall, the present study demonstrated that: (a) the constitutive expression of CYP3A18, CYP3A9, and CYP3A2 does not require the presence of GH, (b) CYP3A18 is more sensitive than CYP3A9 to GH modulation in adult rats; and (c) CYP3A2 is less sensitive to the suppressive influence of GH during the prepubertal period than during adult life.
M Kawai; S M Bandiera; T K Chang; G D Bellward
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  59     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-05-17     Completed Date:  2000-05-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1277-87     Citation Subset:  IM    
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
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MeSH Terms
Aging / metabolism
Aryl Hydrocarbon Hydroxylases*
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System / biosynthesis,  genetics*
Gene Expression Regulation, Developmental*
Gene Expression Regulation, Enzymologic*
Growth Hormone / physiology*
Liver / enzymology*,  growth & development
Oxidoreductases, N-Demethylating / biosynthesis,  genetics
Rats, Sprague-Dawley
Sex Factors
Steroid Hydroxylases / biosynthesis,  genetics*
Reg. No./Substance:
9002-72-6/Growth Hormone; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.-/Steroid Hydroxylases; EC Hydrocarbon Hydroxylases; EC P-450 CYP3A; EC hormone 6-beta-hydroxylase; EC 1.5.-/Oxidoreductases, N-Demethylating

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