Thangavel Chellappagounder, Dhir Ravindra N, Volgin Denys V, Shapiro Bernard H
Laboratories of Biochemistry, Univeristy of Pennsylvania, School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104-6048, USA.
Biochem Pharmacol. 2007 Nov 15;74(10):1476-84. doi: 10.1016/j.bcp.2007.07.035. Epub 2007 Jul 31.
CYP2C11, the most commonly expressed isoform of cytochrome P450 in male rat liver, was measured in spleen, thymus and bone marrow by quantitative real-time PCR and enhanced Western blotting. CYP2C11 concentrations in the lymphoid tissues were a fraction of that observed in liver, but like the liver, were sexually dimorphic (M>F) with mRNA and protein levels in agreement. Although the response to hypophysectomy varied according to tissue and sex, expression levels of CYP2C11 in all measured tissues remained greater in males. Further differences in CYP2C11 expression between liver and lymphoid tissue were observed following restoration of the circulating masculine growth hormone profile in hypophysectomized rats. In contrast to the liver where the renaturalized growth hormone profile elevated CYP2C11 expression in both sexes, the response was opposite in spleen and thymus with isoform concentrations declining in both sexes. Lastly, the divergent response of CYP2C11 between the liver and immune system was examined in cultured splenocytes exposed to different mitogens. In contrast to the dramatic depletion of CYP2C11 reported in proliferating hepatocytes, mitogen-stimulation resulted in a significant elevation in splenocyte CYP2C11 expression. In summary, we report for the first time that thymus, spleen and bone marrow express, albeit nominal, sex-dependent levels of CYP2C11 (M>F) whose regulation appears to be under some hormonal control, but very different from that of the hepatic isoform.
CYP2C11是雄性大鼠肝脏中最常表达的细胞色素P450同工型，通过定量实时PCR和增强型蛋白质印迹法在脾脏、胸腺和骨髓中进行检测。淋巴组织中CYP2C11的浓度仅为肝脏中的一小部分，但与肝脏一样，具有性别差异（雄性>雌性），mRNA和蛋白质水平一致。虽然垂体切除术后的反应因组织和性别而异，但所有测量组织中CYP2C11的表达水平在雄性中仍然更高。在垂体切除的大鼠中恢复循环中的雄性生长激素水平后，观察到肝脏和淋巴组织中CYP2C11表达的进一步差异。与肝脏中恢复生长激素水平会使两性的CYP2C11表达升高相反，脾脏和胸腺中的反应则相反，两性的同工型浓度均下降。最后，在暴露于不同促细胞分裂剂的培养脾细胞中研究了肝脏和免疫系统中CYP2C11的不同反应。与增殖肝细胞中报道的CYP2C11显著减少相反，促细胞分裂剂刺激导致脾细胞CYP2C11表达显著升高。总之，我们首次报道胸腺、脾脏和骨髓表达了尽管含量很低但具有性别依赖性的CYP2C11水平（雄性>雌性），其调节似乎受某些激素控制，但与肝脏同工型的调节非常不同。
