Journal
DRUG METABOLISM AND DISPOSITION
Volume 36, Issue 9, Pages 1737-1739Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/dmd.108.020610
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- NATIONAL CENTER FOR COMPLEMENTARY &ALTERNATIVE MEDICINE [R21AT001376] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [T32ES007126] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM061188] Funding Source: NIH RePORTER
- NCCIH NIH HHS [AT 001376] Funding Source: Medline
- NIEHS NIH HHS [ES 007126] Funding Source: Medline
- NIGMS NIH HHS [GM 61188] Funding Source: Medline
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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.
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