Sarlis N J, Gourgiotis L
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 435, Houston, TX 77030-4009, USA.
Curr Drug Targets Immune Endocr Metabol Disord. 2005 Dec;5(4):439-48. doi: 10.2174/156800805774912971.
Cytochrome P450 (CYP) is a group of enzymes that metabolize drugs to a more water-soluble form, rendering them available for renal excretion. The major site of CYP expression is the liver. Nearly 50% of all medications currently on the market are metabolized by the enzyme CYP3A4, while metabolism of another 35-40% occurs through enzymes CYP1A2, CYP2C19, CYP2D6, CYP3A5 CYP3A6, and CYP3A7. Here, we summarize the current knowledge of the effects of hormones on the CYP family. The term "hormone" is used in its broad sense and includes products of the major endocrine glands (i.e., thyroid, adrenals, gonads, pancreas) and compounds that are not classically considered hormones, such as neurogenic amines, cytokines, interleukins, and eicosanoids. In addition, we comment on the effects on CYP expression of states associated with profound hormonal changes, such as pregnancy, malnutrition, obesity, diabetes mellitus, systemic inflammation, and conditions of altered extracellular fluid volume or osmolality. Available data are limited and are derived primarily from in vitro and animal studies. Moreover, the picture is obscured by conflicting results among studies and the complexity of the regulation of the expression and activity of elements of the CYP system. While the clinical significance of hormonal effects on the CYP system remains to be determined, we anticipate that such effects will be most pertinent to drugs with a narrow therapeutic range. Further research is needed to determine the scope and significance of these effects in view of rapid advances in the field of pharmacogenomics and the ever-increasing number of drugs available for therapeutic use.
细胞色素P450（CYP）是一组将药物代谢为更易溶于水的形式，使其能够通过肾脏排泄的酶。CYP表达的主要部位是肝脏。目前市场上近50%的药物由CYP3A4酶代谢，另外35%-40%的药物代谢则通过CYP1A2、CYP2C19、CYP2D6、CYP3A5、CYP3A6和CYP3A7酶进行。在此，我们总结了目前关于激素对CYP家族影响的知识。术语“激素”在此处使用其广义，包括主要内分泌腺（即甲状腺、肾上腺、性腺、胰腺）的产物以及那些传统上不被视为激素的化合物，如神经源性胺类、细胞因子、白细胞介素和类二十烷酸。此外，我们还评论了与深刻激素变化相关的状态对CYP表达的影响，如妊娠、营养不良、肥胖、糖尿病、全身炎症以及细胞外液量或渗透压改变的情况。现有数据有限，主要来自体外和动物研究。此外，由于研究结果相互矛盾以及CYP系统各元素表达和活性调节的复杂性，情况变得模糊不清。虽然激素对CYP系统影响的临床意义仍有待确定，但我们预计这种影响对于治疗窗狭窄的药物最为相关。鉴于药物基因组学领域的快速进展以及可用于治疗的药物数量不断增加，需要进一步研究以确定这些影响的范围和意义。
