Pitrolo D A, Rumbaugh R C, Colby H D
Drug Metab Dispos. 1979 Jan-Feb;7(1):52-6.
In young (25-day-old) guinea pigs, adrenal and hepatic benzo[a]pyrene (BP) hydroxylase activities were similar but the rates of ethylmorphine (EM) demethylation were greater in adrenals than liver. Between 25 and 50 days of age no sex differences in adrenal or hepatic enzyme activities were demonstrable. The rates of adrenal BP and EM metabolism increased with age in guinea pigs of both sexes; activities reached significantly higher levels in males than females. In contrast, hepatic metabolism of BP and EM declined with maturation and activities were similar in males and females at all ages. Neither microsomal cytochrome P-450 concentrations no NADPH-cytochrome c reductase activities correlated with the maturational changes or sex differences in xenobiotic metabolism. Adrenal microsomal steroid 21-hydroxylase activity did not change significantly with aging and was not sex-dependent. The results indicate that opposite changes occur in adrenal and hepatic xenobiotic metabolism as a function of aging, resulting in substantially greater adrenal than hepatic activity in sexually mature animals. The data also suggest that adrenal microsomal drug and steroid metabolism are independently regulated.
在幼年(25日龄)豚鼠中,肾上腺和肝脏的苯并[a]芘(BP)羟化酶活性相似,但肾上腺中N-乙基吗啡(EM)去甲基化速率高于肝脏。在25至50日龄之间,肾上腺或肝脏酶活性无明显性别差异。两性豚鼠肾上腺中BP和EM的代谢速率均随年龄增长而增加;雄性豚鼠的活性水平显著高于雌性。相反,肝脏中BP和EM的代谢随成熟而下降,且各年龄段雄性和雌性的活性相似。微粒体细胞色素P-450浓度和NADPH-细胞色素c还原酶活性均与异源物质代谢的成熟变化或性别差异无关。肾上腺微粒体类固醇21-羟化酶活性不随年龄显著变化,也无性别依赖性。结果表明,随着年龄增长,肾上腺和肝脏异源物质代谢发生相反变化,导致性成熟动物肾上腺活性显著高于肝脏。数据还表明,肾上腺微粒体药物和类固醇代谢受独立调节。