Shapiro B H, Szczotka S M
Br J Pharmacol. 1984 Jan;81(1):49-54. doi: 10.1111/j.1476-5381.1984.tb10742.x.
Mice of the Crl:CD-1 (ICR)BR strain exhibit a sexual dimorphism in hexobarbitone metabolism and action. Compared to females, males have a lower Vmax and a higher Km for hepatic microsomal hexobarbitone hydroxylase. In agreement with the enzyme studies, hexobarbitone-induced sleeping times were greater for males than for females. Results from experiments measuring hexobarbitone metabolism and action in castrate, testosterone and gonadotropin-treated mice indicate that the sexual differences in drug metabolism and action found in Crl:CD-1 (ICR)BR mice are due to the normally repressive effects of testicular androgens on the activities of the hepatic mono-oxygenases. These findings are in dramatic contrast to studies with rats where it has been shown that androgens induce mono-oxygenases. Furthermore, in the case of the mouse, changes in the activity of hexobarbitone hydroxylase in response to alterations in androgen levels require weeks, while in the rat, androgenic-induced changes are apparent within a matter of days.
Crl:CD-1(ICR)BR品系的小鼠在己巴比妥代谢及作用方面表现出性二态性。与雌性相比，雄性肝微粒体己巴比妥羟化酶的Vmax较低而Km较高。与酶学研究结果一致，己巴比妥诱导的睡眠时间雄性比雌性更长。对去势、睾酮和促性腺激素处理的小鼠进行己巴比妥代谢及作用测量的实验结果表明，Crl:CD-1(ICR)BR小鼠中发现的药物代谢及作用的性别差异是由于睾丸雄激素对肝单加氧酶活性的正常抑制作用。这些发现与对大鼠的研究形成了鲜明对比，在大鼠研究中已表明雄激素可诱导单加氧酶。此外，就小鼠而言，己巴比妥羟化酶活性随雄激素水平变化而改变需要数周时间，而在大鼠中，雄激素诱导的变化在数天内就很明显。
