Yamazoe Y, Murayama N, Shimada M, Kato R
Department of Pharmacology, School of Medicine, Keio, Tokyo, Japan.
Biochem Biophys Res Commun. 1989 Apr 28;160(2):609-14. doi: 10.1016/0006-291x(89)92476-5.
Mechanism of developmental suppression of cytochrome P-450 (P-450) in rat livers was studied using Western blots. The contents of phenobarbital (PB)-inducible P-450b and P-450e, expressed constitutively in livers, were higher in neonate than in adult rats. The contents were also 10 approximately 50 fold higher in hypophysectomized than in intact adult male rats. Administration of L-triiodothyronine (T3, 50 micrograms/kg) or human growth hormone (4 U/kg) reversed almost completely the increased amounts of P-450b and P-450e. T3-induced suppression was also observed on two other neonatal P-450s (P-450 6 beta-1 and P-448-H), which are expressed in neonatal periods in livers. The postnatal developmental profiles of hepatic P-450b were correlated inversely with that of serum free T3 level in rats reported (Walker et al. (1980) Pediat. Res. 14, 249). These results suggest, in addition to pituitary growth hormone (Yamazoe et al. (1987) J. Biol. Chem. 262, 7423), the possible involvement of T3 on the suppressive regulation of PB-inducible and other neonatal P-450s.
利用蛋白质免疫印迹法研究了大鼠肝脏中细胞色素P - 450(P - 450)发育抑制的机制。肝脏中组成性表达的苯巴比妥(PB)诱导型P - 450b和P - 450e的含量,新生大鼠高于成年大鼠。垂体切除的成年雄性大鼠中这些含量也比完整成年雄性大鼠高约10至50倍。给予L - 三碘甲状腺原氨酸(T3,50微克/千克)或人生长激素(4单位/千克)几乎完全逆转了P - 450b和P - 450e含量的增加。在另外两种在新生大鼠肝脏中表达的新生期P - 450(P - 450 6β - 1和P - 448 - H)上也观察到了T3诱导的抑制作用。已报道大鼠肝脏中P - 450b的出生后发育情况与血清游离T3水平呈负相关(Walker等人,(1980年)《儿科研究》14卷,第249页)。这些结果表明,除了垂体生长激素外(Yamazoe等人,(1987年)《生物化学杂志》262卷,第7423页),T3可能参与了对PB诱导型和其他新生期P - 450的抑制调节。