Abstract
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.
Footnotes
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This study was supported by the National Institutes of Health (Grants GM 61188 and AT 001376) and by the National Institute of Environmental Health Sciences (Grant ES 007126).
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.108.020610.
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ABBREVIATIONS: UGT, uridine diphosphoglucuronosyltransferase; HPLC, high-performance liquid chromatography; MPAG, mycophenolic acid phenol glucuronide.
- Received February 29, 2008.
- Accepted May 29, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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