Academic journal article Environmental Health Perspectives

Developmental Increases in Rat Hepatic Microsomal UDP-Glucuronosyltransferase Activities toward Xenoestrogens and Decreases during Pregnancy. (Articles)

Academic journal article Environmental Health Perspectives

Developmental Increases in Rat Hepatic Microsomal UDP-Glucuronosyltransferase Activities toward Xenoestrogens and Decreases during Pregnancy. (Articles)

Article excerpt

Xenoestrogens, such as bisphenol A and diethylstilbestrol, are glucuronidated by an isoform of UDP-glucuronosyltransferase named UGT2B1 in the livers of adult male rats. In this study, we found that nonylphenol and octylphenol are also conjugated with glucuronic acid by adult rat liver microsomes. Although UDP-glucuronosyltransferase activities toward these xenoestrogens were not detected in the fetal rat liver, a linear increase in enzymatic activities during neonatal development was observed. At 3 weeks after birth, the activities had reached the same level as that of adult rats. The protein and mRNA contents of UGT2B1 also were not detected in the fetal rat liver, but a developmental increase in newborn rat liver was detected by Western and Northern blotting analysis. Additionally, rat hepatic microsomal UDP-glucuronosyltransferase activities toward these xenoestrogens were reduced by about half during pregnancy of mother rats. The results suggest that the reproductive organs of fetal and early-stage neonatal rats, which are sensitive to sex hormones, face a high risk of exposure to free active xenoestrogens. Key words: bisphenol A, diethylstilbestrol, fetus, glucuronidation, nonylphenol, pregnancy, rats, UDP-glucuronosyltransferase, xenoestrogens. Environ Health Perspect 110:193-196 (2002). [Online 18 January 2002]

http://ehpnet1.niehs.nih.gov/does/2002/110p193-196matsumoto/ abstract.html

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Many substances are considered environmental estrogens, including pesticides, pollutants, and various chemicals (1). Bisphenol A (BPA), which is a monomer of polycarbonate plastics and a constituent of epoxy and polystyrene resins that are used extensively in the food-packaging industry and dentistry, and alkylphenols such as nonylphenol and octylphenol, which are degraded from detergents (alkylphenol polyethoxylates) and polystyrenes, have been reported to be environmental pollutants and have estrogenic activity (2-4). Prenatal treatment with bisphenol A (2.4 mg/kg for 7 days in pregnant CF-1 mice) significantly reduced the number of days between vaginal opening and first vaginal estrus in females that are located between two female fetuses (5). Exposure to nonylphenol also reduces testis growth in trout (6) and accelerates the vaginal opening in [F.sub.1], [F.sub.2], and [F.sub.3] generations of rats ([F.sub.1] is the first generation produced by crossing two parental lines; [F.sub.2] and [F.sub.3] are the second and third generations) (7). In addition, neonatal exposure to octylphenol can reduce the testicular sizes of animals (8). Recently, we reported that BPA and diethylstilbestrol (DES) were glucuronidated by an isoform of UDP-glucuronosyltransferase (Enzyme Classification 2.4.1.17), UGT2B1, in the rat liver (9). Glucuronidation activities of xenoestrogens in fetal, neonatal, and pregnant rats are considered to be of critical importance.

In this study, we found that although rat liver microsomal UDP-glucuronosyltransferase activities toward xenoestrogens were absent in the fetus, they increased developmentally in the neonate, even though they were reduced in the pregnant rat.

Materials and Methods

Cholic acid, purchased from Nissui Yakuhin Co. (Tokyo, Japan), was further purified and converted to its sodium salt (10). UDP-glucuronic acid was obtained from Nakarai Yakuhin Co. (Kyoto, Japan). Bisphenol A, DES, DES-glucuronide, testosterone, estradiol, and estradiol-glucuronide were obtained from Sigma (St. Louis, MO). Other reagents were of the highest grade available.

Preparation of microsomes from rat tissues. Pregnant Wistar rats (8-10 weeks of age) were purchased from Sankyo Lab Co. (Sapporo, Japan). Animals were individually housed under standard conditions and maintained ad libitum on a standard diet. The mother and newborn rats were killed by cervical dislocation, and the liver was minced and homogenized with 4 volumes of 0.15 M KCl solution containing 1 mM EDTA. …

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