Adams J B, Phillips N S, Hall R
School of Biochemistry, University of New South Wales, Sydney, Australia.
Mol Cell Endocrinol. 1988 Aug;58(2-3):231-42. doi: 10.1016/0303-7207(88)90159-1.
The metabolism of 17 beta-estradiol in both estrogen receptor positive and negative human breast cancer cell lines has been compared. Initial experiments in which confluent cells were exposed to 1 nM [3H]17 beta-estradiol for 24 h, revealed that the main metabolites formed by estrogen receptor positive MCF-7 and ZR-75-1 cells were 17 beta-estradiol-3-sulfate (together with lesser amounts of estrone sulfate) and estrone. In estrogen receptor negative cell lines, production of estrogen sulfates was either significantly lower (MDA-MB-231 cells) than receptor positive cells, or failed to be produced at all (MDA-MB-330 cells). In both these receptor negative cell lines, production of estrone was significantly higher than in receptor positive cells. Accumulation of estrogen sulfates resulted from attainment of a steady state between synthesis catalysed by estrogen sulfotransferase and degradation catalysed by estrogen sulfatase. The former was present in the cytosol and showed a very high affinity for 17 beta-estradiol and estrone (low nM range). Complex initial velocity versus estrogen substrate curves were obtained with enzyme purified 106-fold by affinity chromatography. Such curves were consistent with a rate equation of degree 3 or 4 and suggest the presence of cooperatively linked dependent binding sites.
对雌激素受体阳性和阴性的人乳腺癌细胞系中17β-雌二醇的代谢情况进行了比较。最初的实验是将汇合的细胞暴露于1 nM [3H]17β-雌二醇中24小时，结果显示雌激素受体阳性的MCF-7和ZR-75-1细胞形成的主要代谢产物是17β-雌二醇-3-硫酸盐（以及少量的硫酸雌酮）和雌酮。在雌激素受体阴性的细胞系中，雌激素硫酸盐的产生要么显著低于受体阳性细胞（MDA-MB-231细胞），要么根本不产生（MDA-MB-330细胞）。在这两种受体阴性的细胞系中，雌酮的产生都显著高于受体阳性细胞。雌激素硫酸盐的积累是由雌激素磺基转移酶催化的合成与雌激素硫酸酯酶催化的降解之间达到稳态所致。前者存在于胞质溶胶中，对17β-雌二醇和雌酮表现出非常高的亲和力（低纳摩尔范围）。通过亲和层析纯化106倍的酶得到了复杂的初速度与雌激素底物曲线。这些曲线与三阶或四阶速率方程一致，表明存在协同连接的依赖结合位点。
