title: Effect of neonatal exposure of 17beta-estradiol and tamoxifen on hepatic CYP3A activity at developmental periods in rats.
abstract: We evaluated hepatic CYP3A activity during development in male and female rats and the effect of neonatal exposure of 17beta-estradiol and tamoxifen. In untreated and olive oil-treated (control) rats, hepatic CYP3A activities evaluated by erythromycin metabolism in vitro increased several-fold from age 2 to 9 weeks in males. In contrast, activity in females remained at a low and constant level from 2 to 15 weeks. Exposure of 17beta-estradiol to neonates at a dose of 10 micromol/kg daily for 3 days on day 1-3 (approximately) or 4-6 (approximately) after birth significantly increased hepatic CYP3A activity during the developmental period in both males and females, and a greater influence was observed in females exposed during days 4-6 (approximately). Pubertal exposure of 17beta-estradiol (7-weeks old, 10 micromol/kg daily for 3 days) also increased hepatic CYP3A activity, but only in females. Neonatal exposure to tamoxifen (10 micromol/kg daily for 3 days) showed no appreciable effect in either males or females. In conclusion, a marked sex-difference was observed in hepatic CYP3A activity, and exposure of 17beta-estradiol to neonates increased hepatic CYP3A activity during the developmental period, especially in female rats.
authors.affiliation: Department of Pharmaceutics and Therapeutics, Programs for Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University.
authors.forename: Teruo
authors.initials: T
authors.lastname: Murakami
authors.forename: Akiko
authors.initials: A
authors.lastname: Sato
authors.forename: Michiyasu
authors.initials: M
authors.lastname: Inatani
authors.forename: Hanao
authors.initials: H
authors.lastname: Sakurai
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yumoto
authors.forename: Junya
authors.initials: J
authors.lastname: Nagai
authors.forename: Mikihisa
authors.initials: M
authors.lastname: Takano
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D004917:Erythromycin / Q000493:pharmacokinetics; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D012741:Sexual Maturation / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D004958:Estradiol; D004917:Erythromycin; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating