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Drug Metabolism and Disposition Fast Forward
First published on May 30, 2008; DOI: 10.1124/dmd.108.020610

0090-9556/08/3609-1737-1739$20.00
DMD 36:1737-1739, 2008

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SHORT COMMUNICATION

Androgen Regulation of Renal Uridine Diphosphoglucuronosyltransferase 1A1 in Rats

Stephan T. Stern, Melanie N. Tallman, Kristini K. Miles, Joseph K. Ritter, and Philip C. Smith

Department of Drug Delivery and Disposition, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina (S.T.S, M.N.T., P.C.S.); and Department of Pharmacology and Toxicology, School of Medicine, University of Virginia Commonwealth, Richmond, Virginia (K.K.M., J.K.R.)

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.

Address correspondence to: Dr. Philip C. Smith, School of Pharmacy, CB 7360, University of North Carolina, Chapel Hill, NC 27599-7360. E-mail: pcs{at}email.unc.edu






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