HUMAN LIVER DEHYDROEPIANDROSTERONE SULFOTRANSFERASE - NATURE AND EXTENT OF INDIVIDUAL VARIATION
HUMAN LIVER DEHYDROEPIANDROSTERONE SULFOTRANSFERASE - NATURE AND EXTENT OF INDIVIDUAL VARIATION
复制标题
DOI：
10.1038/clpt.1993.181
复制
发表时间：
1993-11-01
影响因子：
6.7
通讯作者：
WEINSHILBOUM, RM
中科院分区：
文献类型：
--
作者：
AKSOY, IA;SOCHOROVA, V;WEINSHILBOUM, RM
脱氢表雄酮磺基转移酶 (DHEA ST) 催化 DHEA、雌酮和雌二醇等类固醇激素的硫酸化。作为人类 DHEA ST 药物遗传学研究的第一步，我们测量了 94 个人类肝组织样本中 DHEA ST 酶活性和热稳定性的个体差异，其中 39 个来自肝功能研究正常的患者。酶活性水平和热稳定性与-80℃下组织储存时间或患者年龄均不显着相关。此外，这些样本中的 DHEA ST 活性不存在性别依赖性差异。 DHEA ST 酶活性变化 4.6 倍，所有样本中的平均值为 317 +/- 100 单位/克组织（平均值 +/- SD），来自肝功能正常的患者的 39 个样本子集中的平均值为 318 +/- 104 单位/克。整个 94 个样本组和 39 个样本子集的 DHEA ST 活性频率分布均为双峰，分别有 25% 和 21% 属于高活性子组。当分别评估男性和女性患者的样本数据并且仅检查白人患者的数据时，证实了这种高活性亚组的存在。肝脏中具有高水平 DHEA ST 酶活性且该活性范围为 4.6 倍的受试者亚组的存在，对内源性和外源性类固醇激素的硫酸盐结合的个体差异产生影响，并提高了对人类这种重要酶进行药物遗传学调节的可能性。
Dehydroepiandrosterone sulfotransferase (DHEA ST) catalyzes the sulfation of steroid hormones such as DHEA, estrone, and estradiol. As a first step in pharmacogenetic studies of DHEA ST in humans, we measured individual variation in DHEA ST enzymatic activity and thermal stability in 94 samples of human hepatic tissue, 39 of which were from patients with normal liver function studies. Neither level of enzyme activity nor thermal stability were significantly correlated with either time of tissue storage at -80-degrees-C or patient age. In addition, there were no gender-dependent differences in DHEA ST activity in these samples. DHEA ST enzymatic activity varied 4.6-fold, with a mean value of 317 +/- 100 units/gm tissue (mean +/- SD) in all samples and 318 +/- 104 units/gm in the subset of 39 samples from patients with normal hepatic function studies. Frequency distribution of DHEA ST activity for both the entire group of 94 samples and the subset of 39 were bimodal, with 25% and 21% included in a high activity subgroup, respectively. The presence of this high activity subgroup was confirmed when data for samples from male and female patients were evaluated separately and when only data for white patients were examined. The existence of a subgroup of subjects with a high level of DHEA ST enzymatic activity in liver and a 4.6-fold range in this activity have implications for individual differences in the sulfate conjugation of endogenous and exogenously administered steroid hormones and raise the possibility of pharmacogenetic regulation of this important enzyme in humans.