Further studies on the persistence of neonatal androgen imprinting on sex-specific cytochrome P-450, testosterone and drug oxidations.
Neonatal castration completely suppressed the expression of P-450-male and expressed P-450-female; and testosterone treatment in a neonatal period partially reversed the effect of castration, i.e., neonatal imprinting (Kamataki et al., 1984; Waxman et al., 1985). In the present communication, we investigate the reversibility and persistency of neonatal imprinting on the expression of P-450-male and P-450-female. To our surprise, testosterone treatment at adulthood (8 weeks old) caused full expression of P-450-male and restored the activities of 2 alpha- and 16 alpha-testosterone hydroxylases in neonatally castrated rats. The levels of ethylmorphine N-demethylation, propoxycoumarin O-depropylation and benzo(a)pyrene hydroxylation were increased to the levels of adult male rats by adult testosterone-treatment. Moreover, treatment with testosterone of neonatally castrated rats at the age of 19 weeks did not cause a complete recovery of P-450-male content and drug-metabolizing activities. Testosterone administration into neonatal female rats did not significantly alter the contents of sex-dependent cytochrome P-450 and drug and steroid metabolizing activities in adulthood. Additional testosterone treatment in adulthood only slightly affected these parameters. All these results indicate that neonatal androgen imprinting on sex-dependent cytochrome P-450 and drug and steroid metabolizing activities in rat liver microsomes is not a permanent programming process and is modified by the presence and absence of sex-steroid hormones.
Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.
M
M
Shimada
N
N
Murayama
Y
Y
Yamazoe
T
T
Kamataki
R
R
Kato
D000728:Androgens / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009919:Orchiectomy; D010052:Ovariectomy; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D013739:Testosterone / Q000378:metabolism*
D000728:Androgens; D004364:Pharmaceutical Preparations; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System