Development of UDP-glucuronosyltransferase activity toward digitoxigenin-monodigitoxoside in neonatal rats

JB Watkins and CD Klaassen

Glucuronidation is low or undetectable in embryonic and early fetal tissues and changes to adult levels at rates depending on the acceptor, tissue, and species. Because other data indicate there may be a specific UDP-glucuronosyltransferase (GT) in the liver of adult rats that glucuronidates digitoxigenin-monodigitoxoside (DIG), the development of GT activity in neonatal rats toward DIG was compared with that of other acceptors. Conjugation of p-nitrophenol and 1- naphthol was higher at birth and decreased to adult levels by 20 days of age. Glucuronidation of chloramphenicol, morphine, valproic acid, and bilirubin increased from birth to adult activity by 20 days of age. Conjugation of phenolphthalein, estrone, and diethylstilbestrol was low in 1-day-old rats and higher than adult in 20-day-old animals. In contrast, glucuronidation of DIG was barely detectable (9% of adult) in 20-day-old rats. The concentration of UDP-glucuronic acid was 50% of adult levels at birth and increased to adult values by 10 days of age. Administration of 3-methylcholanthrene on days 6 to 9 after birth significantly stimulated GT activity toward 1-naphthol, p-nitrophenol, and morphine, whereas phenobarbital precociously increased conjugation of chloramphenicol, valproic acid, morphine, and diethylstilbestrol. Pregnenolone-16 alpha-carbonitrile enhanced the development of GT activity toward morphine, chloramphenicol, valproic acid, bilirubin, diethylstilbestrol, and estrone. Glucuronidation of DIG was not increased after 3-methylcholanthrene or phenobarbital, but could be induced after pregnenolone-16 alpha-carbonitrile to 7% of adult values in 10-day-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 13, Issue 2, pp. 186-191, 03/01/1985
Copyright © 1985 by American Society for Pharmacology and Experimental Therapeutics