Androgen regulation of renal uridine diphosphoglucuronosyltransferase 1A1 in rats.
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.
Stern
Stephan T
ST
School of Pharmacy, CB 7360, University of North Carolina, Chapel Hill, NC 27599-7360, USA.
Tallman
Melanie N
MN
Miles
Kristini K
KK
Ritter
Joseph K
JK
Smith
Philip C
PC
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099148:UGT1A1 Enzyme
D000728:Androgens; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme