Effect of neonatal exposure of 17beta-estradiol and tamoxifen on hepatic CYP3A activity at developmental periods in rats.
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.
Murakami
Teruo
T
Department of Pharmaceutics and Therapeutics, Programs for Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University.
Sato
Akiko
A
Inatani
Michiyasu
M
Sakurai
Hanao
H
Yumoto
Ryoko
R
Nagai
Junya
J
Takano
Mikihisa
M
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*
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