Androgen Regulation of Renal Uridine Diphosphoglucuronosyltransferase 1A1 in Rats

Many phase I and II enzymes are under hormonal regulation, resulting in sex-related expression patterns. This sex-related enzyme expression can result in differential metabolism of physiologically active endogenous substances, altered xenobiotic clearance, and differences in susceptibility to drug t...

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Published inDrug metabolism and disposition Vol. 36; no. 9; pp. 1737 - 1739
Main Authors STERN, Stephan T, TALLMAN, Melanie N, MILES, Kristini K, RITTER, Joseph K, SMITH, Philip C
Format Journal Article
LanguageEnglish
Published Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.09.2008
Subjects
Androgens - pharmacology
Animals
Biological and medical sciences
Blotting, Western
Female
Glucuronosyltransferase - metabolism
Kidney - drug effects
Kidney - enzymology
Male
Medical sciences
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Vertebrata
Mammalia
Urinary system
Androgen
Rat
Animal
Rodentia
Uridine
Sex steroid hormone
Pyrimidine nucleoside
Kidney
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Summary:Many phase I and II enzymes are under hormonal regulation, resulting in sex-related expression patterns. This sex-related enzyme expression can result in differential metabolism of physiologically active endogenous substances, altered xenobiotic clearance, and differences in susceptibility to drug toxicities. Treatment of female Sprague-Dawley (SD) rats with 5 mg testosterone propionate/kg/day, 2 ml/kg s.c. for 8 days resulted in induction of renal uridine diphosphoglucuronosyltransferase (UGT) 1A1, as determined by immunoblot and probe substrate activity. Glucuronidation activity for mycophenolic acid, a substrate for rat UGT1A1, 1A6, and 1A7, was significantly elevated approximately 2-fold in renal microsomes from testosterone propionate-treated animals. Protein expression of rat UGT1A1 was also dramatically increased, whereas 1A6 and 1A7 remained unchanged as a result of treatment. Male SD rats were determined to express greater renal UGT1A1 than age-matched female rats. These data support the androgen regulation of rat renal UGT1A1.
ISSN:0090-9556
1521-009X
DOI:10.1124/dmd.108.020610