Sharma Meena R, Dworakowski Wojciech, Shapiro Bernard H
Laboratories of Biochemistry, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania 19104-6048, USA.
Toxicol Pathol. 2012;40(1):83-92. doi: 10.1177/0192623311425061. Epub 2011 Nov 14.
Adult male and female rat hepatocytes were individually transplanted into the spleens of adult male and female rats. The recipients were euthanized at either eight, sixteen, thirty, or forty-five weeks following transplantation, at which time hepatic and splenic levels of liver-specific rat albumin mRNA as well as sex-dependent transcript levels of CYP2C11, -2C12, -2C7, -2A1, and -3A2-which accounts for > 60% of the total concentration of hepatic constituent cytochrome P450-were determined. Whereas the pre-infused hepatocytes expressed their expected cytochrome P450 sexual dimorphisms (female-specific CYP2C12, male-specific CYP3A2, and female-predominant CYP2A1), their post-transplantational competence now reflected the sexual dimorphisms of the recipient (as observed in the host's liver), which supports the concept that the sex-dependent growth hormone circulating profiles are the determinants regulating the expression levels of hepatic cytochrome P450. Also expressed at normal concentrations in the pre-infused hepatocytes, male-specific CYP2C11 and female-predominant CYP2C7 were inexplicably undetectable in the spleens of both recipient males and females, regardless of the sex of the donor hepatocytes, almost one year after transplantation.
将成年雄性和雌性大鼠的肝细胞分别移植到成年雄性和雌性大鼠的脾脏中。在移植后的8周、16周、30周或45周对受体实施安乐死，此时测定肝脏和脾脏中肝脏特异性大鼠白蛋白mRNA的水平，以及CYP2C11、-2C12、-2C7、-2A1和-3A2的性别依赖性转录水平（CYP3A2占肝脏组成细胞色素P450总浓度的60%以上）。虽然预先注入的肝细胞表现出预期的细胞色素P450性别二态性（雌性特异性CYP2C12、雄性特异性CYP3A2和雌性占主导的CYP2A1），但其移植后的功能现在反映了受体的性别二态性（如在宿主肝脏中观察到的），这支持了以下概念，即性别依赖性生长激素循环谱是调节肝细胞色素P450表达水平的决定因素。在预先注入的肝细胞中也以正常浓度表达的雄性特异性CYP2C11和雌性占主导的CYP2C7，在移植后近一年，无论供体肝细胞的性别如何，在受体雄性和雌性的脾脏中均无法检测到。
