Her C, Szumlanski C, Aksoy I A, Weinshilboum R M
Department of Pharmacology, Mayo Medical School/Mayo Clinic/Mayo Foundation, Rochester, MN 55905, USA.
Drug Metab Dispos. 1996 Dec;24(12):1328-35.
Sulfate conjugation is an important metabolic pathway for many drugs, xenobiotic compounds, and steroid hormones. Human tissues express five cytoplasmic sulfotransferase (ST) enzymes: estrogen ST (EST), dehydroepiandrosterone (DHEA) ST, and three phenol STs (PSTs). Both EST and DHEA ST can catalyze the sulfonation of steroid compounds, including exogenously administered steroids such as ethinyl estradiol. We set out to characterize immunochemically the nature and extent of individual variation in the expression of EST and DHEA ST in the human small intestine after Northern blot analysis had demonstrated that both enzymes were expressed in that tissue. Polyclonal antibodies to human EST and DHEA ST were developed, and Western blot analysis demonstrated that the antibodies were specific. We then performed quantitative Western blots of EST and DHEA ST in 62 samples of human jejunal mucosa. Large individual variations in immunoreactive EST and DHEA ST protein levels were present in those 62 tissue samples. However, there was not a significant correlation between levels of immunoreactive protein for the two enzymes (rs = 0.143, p = 0.262), indicating that EST and DHEA ST in the human jejunum are regulated independently. Furthermore, immunoreactive EST and DHEA ST protein levels in these samples did not differ significantly between the genders, and neither was correlated significantly with time of tissue storage, patient age, or underlying pathology. Frequency distribution histograms of immunoreactive protein values were skewed for both enzymes, and the DHEA ST frequency distribution seemed to be bimodal. These results represent a step toward understanding the molecular basis for individual variation in the expression and function of EST and DHEA ST in the human small intestine.
硫酸结合是许多药物、外源性化合物和甾体激素的重要代谢途径。人体组织表达五种细胞质硫酸转移酶（ST）：雌激素ST（EST）、脱氢表雄酮（DHEA）ST和三种苯酚ST（PST）。EST和DHEA ST都能催化甾体化合物的磺化反应，包括外源性给予的甾体，如乙炔雌二醇。在Northern印迹分析表明这两种酶在人小肠组织中均有表达后，我们着手通过免疫化学方法对人小肠中EST和DHEA ST表达的个体差异的性质和程度进行表征。制备了针对人EST和DHEA ST的多克隆抗体，Western印迹分析表明这些抗体具有特异性。然后我们对62份人空肠黏膜样本进行了EST和DHEA ST的定量Western印迹分析。在这62个组织样本中，免疫反应性EST和DHEA ST蛋白水平存在较大的个体差异。然而，这两种酶的免疫反应性蛋白水平之间没有显著相关性（rs = 0.143，p = 0.262），表明人空肠中的EST和DHEA ST是独立调节的。此外，这些样本中免疫反应性EST和DHEA ST蛋白水平在性别之间没有显著差异，也与组织储存时间、患者年龄或潜在病理状况无显著相关性。两种酶的免疫反应性蛋白值的频率分布直方图均呈偏态，且DHEA ST频率分布似乎呈双峰分布。这些结果朝着理解人小肠中EST和DHEA ST表达和功能个体差异的分子基础迈出了一步。
