PT  - JOURNAL ARTICLE
AU  - Masahiko Kawai
AU  - Stelvio M. Bandiera
AU  - Thomas K. H. Chang
AU  - Frederique M. Poulet
AU  - Paul M. Vancutsem
AU  - Gail D. Bellward
TI  - Modulation of Hepatic CYP2A1, CYP2C11, and CYP3A9 Expression in Adult Rats by Neonatal Administration of Tamoxifen
DP  - 1999 Dec 01
TA  - Drug Metabolism and Disposition
PG  - 1392--1398
VI  - 27
IP  - 12
4099  - http://dmd.aspetjournals.org/content/27/12/1392.short
4100  - http://dmd.aspetjournals.org/content/27/12/1392.full
SO  - Drug Metab Dispos1999 Dec 01; 27
AB  - To examine the effect of neonatal administration of tamoxifen on adult expression of hepatic cytochrome P-450 (CYP) enzymes and steroid 5α-reductase, male and female Sprague-Dawley rats were injected s.c. with tamoxifen (20 μg) or peanut oil (control) once daily at days 1 to 5 of age and sacrificed at 3 months of age. Neonatal tamoxifen treatment did not affect b.wt. or liver weight of adult male and female rats, but decreased testicular weight by approximately 40% in adult male rats. Neonatal administration of tamoxifen decreased hepatic microsomal testosterone 6β- and 7α-hydroxylase activities in adult female rats whereas it did not alter steroid 5α-reductase activity. The same treatment increased testosterone 7α-hydroxylase activity, but did not affect testosterone 6β-hydroxylase or steroid 5α-reductase activity in adult male rats. Immunoblot analysis indicated that neonatal tamoxifen treatment decreased CYP2C11 protein level by 26% and increased CYP2A1 protein content by 2.6-fold in adult male rats, whereas it had no effect on CYP3A or CYP2B protein expression. The reduction in the CYP3A-mediated testosterone 6β-hydroxylase activity in adult female rats was accompanied by a decrease in CYP3A9 mRNA expression. Analysis of serum hormone levels indicated that neonatal exposure to tamoxifen resulted in a decrease in serum 17β-estradiol concentration in adult female rats, whereas it did not alter serum testosterone concentration in adult male rats. In summary, treatment of neonatal rats with tamoxifen produced a long-lasting effect on hepatic CYP2A1, CYP2C11, and CYP3A9 expression in addition to testicular weight and serum 17β-estradiol concentration. The American Society for Pharmacology and Experimental Therapeutics