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
-
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).
-
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
-
doi:10.1124/dmd.108.020610.
-
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
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
