Fishman J, Bradlow H L, Schneider J, Anderson K E, Kappas A
Proc Natl Acad Sci U S A. 1980 Aug;77(8):4957-60. doi: 10.1073/pnas.77.8.4957.
The oxidative metabolism of estradiol was studied in normal men and women by a radiometric procedure that provides information on the totality of the biotransformations concerned. The release of 3H into body water from estradiol labeled with 3H in the 17 alpha, 16 alpha, and C-2 positions permits measurement of the rate and extent of 17 beta-ol oxidation and of the competing hydroxylations at C-2 and 16 alpha, which lead to products with different biologicaly properties. In both men and women the 17 beta-ol oxidation is the most rapid transformation, followed by 2-hydroxylation and finally by 16 alpha-hydroxylation. Hydroxylation at C-2 predominates by a faccto of 2-4 over 16 alpha-hydroxylation. In men a large fraction (37%) of the substrate is unmetabolized at any of the three sites and is not excreted in urine; in women the corresponding fraction is only 18%. The estradiol fraction that does undergo metabolism is hydroxylated at C-2 vs. 16 alpha to a greater extent in women than in men. These major sex differences in the metabolism of estradiol in the human may have an important influence on the expression of the biological actions of the hormone. The radiometric technique used in this study can be generally applied to study the oxidative transformations of hormones, drugs, and other exogenous chemical that can be specifically labeled at reactive sites.
通过一种能提供有关相关生物转化总体信息的放射性测量方法，对正常男性和女性体内雌二醇的氧化代谢进行了研究。从在17α、16α和C - 2位标记有³H的雌二醇中³H释放到体内水中的情况，可用于测量17β - 醇氧化以及C - 2和16α位竞争性羟基化的速率和程度，这些羟基化会产生具有不同生物学特性的产物。在男性和女性中，17β - 醇氧化都是最快速的转化过程，其次是2 - 羟基化，最后是16α - 羟基化。C - 2位的羟基化比16α - 羟基化占主导地位，二者比例为2至4比1。在男性中，很大一部分（37%）底物在这三个位点中的任何一个都未被代谢，且未通过尿液排出；在女性中，相应比例仅为18%。确实发生代谢的雌二醇部分在女性中C - 2位羟基化相对于16α位的程度比男性更大。人类雌二醇代谢中的这些主要性别差异可能对该激素生物学作用的表达有重要影响。本研究中使用的放射性测量技术通常可应用于研究激素、药物和其他可在反应位点进行特异性标记的外源性化学物质的氧化转化。
