Androgen Regulation of Renal Uridine Diphosphoglucuronosyltransferase 1A1 in Rats

• Published in: Drug metabolism and disposition Vol. 36; no. 9; pp. 1737 - 1739
• Main Authors: STERN, Stephan T, TALLMAN, Melanie N, MILES, Kristini K, RITTER, Joseph K, SMITH, Philip C
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.09.2008
• Subjects: Androgens - pharmacology; Animals; Biological and medical sciences; Blotting, Western; Female; Glucuronosyltransferase - metabolism; Kidney - drug effects; Kidney - enzymology; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Vertebrata; Mammalia; Urinary system; Androgen; Rat; Animal; Rodentia; Uridine; Sex steroid hormone; Pyrimidine nucleoside; Kidney
• DOI: 10.1124/dmd.108.020610
• ISSN: 0090-9556

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.