Effect of adrenalectomy on expression and induction of UDP-glucuronosyltransferase 1A6 and 1A7 in rats.
Uridine 5'-diphosphate (UDP)-glucuronosyltransferase 1A (UGT1A), which catalyzes major phase II reactions, is regulated by endogenous and exogenous factors via nuclear receptors such as the aryl hydrocarbon receptor (AhR). Glucocorticoid, one of the adrenocortical hormones, regulates AhR and UGT1A expression. We examined the effects of adrenalectomy on the expression and induction of UGT1A via AhR in the rat liver and small intestine. Rats were adrenalectomized bilaterally (ADX) or sham-operated (SHAM) and received intraperitoneal treatment with β-naphthoflavone (BNF) for 4 d. Hepatic UGT1A6 and UGT1A7 mRNA levels were altered by ADX (0.1-fold and 1.6-fold, respectively). BNF treatment increased UGT1A6 and UGT1A7 mRNA expression and the intrinsic clearance of acetaminophen (APAP) glucuronidation, which is primarily catalyzed by UGT1A6 and UGT1A7, in both SHAM and ADX rats. Therefore, ADX rats maintained a functional AhR signaling pathway in the presence of BNF, expressed UGT1A6 and UGT1A7 mRNA, and showed APAP glucuronidation, namely induction by BNF via AhR was not abolished. Our results indicate that adrenal-dependent factors such as glucocorticoids are partially involved in the basal regulation of UGT1A6 and UGT1A7 transcription.
Department of Pharmaceutics, Faculty of Pharmacy, Meijo University.
Yukiko
Y
Sakakibara
Miki
M
Katoh
Masaya
M
Suzuki
Ryoko
R
Kawabe
Keisuke
K
Iwase
Masayuki
M
Nadai
D000082:Acetaminophen / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D014453:Glucuronosyltransferase / Q000096:biosynthesis*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000378:metabolism; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors; D019324:beta-Naphthoflavone / Q000494:pharmacology
D018336:Receptors, Aryl Hydrocarbon; D000082:Acetaminophen; D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase; C107611:UDP-glucuronosyltransferase, UGT1A7