RT Journal Article
SR Electronic
T1 Androgen Regulation of Renal Uridine Diphosphoglucuronosyltransferase 1A1 in Rats
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1737
OP 1739
DO 10.1124/dmd.108.020610
VO 36
IS 9
A1 Stephan T. Stern
A1 Melanie N. Tallman
A1 Kristini K. Miles
A1 Joseph K. Ritter
A1 Philip C. Smith
YR 2008
UL http://dmd.aspetjournals.org/content/36/9/1737.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics