Milewich L, Porter J C
J Clin Endocrinol Metab. 1987 Jul;65(1):164-9. doi: 10.1210/jcem-65-1-164.
The enzymatic hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate to estrone and dehydroisoandrosterone, respectively, was studied in cells that were derived from four different malignant tumors of the lower reproductive tract of women, viz. a squamous cell vaginal carcinoma, an ovarian carcinoma, and two endometrial adenocarcinomas. These cells had the capacity to hydrolyze both steroid sulfoconjugates. Estrone sulfate was more efficient as a substrate than dehydroepiandrosterone sulfate, since the amount of product formed from estrone sulfate was approximately 3-fold greater than that formed from dehydroepiandrosterone sulfate. Some kinetic parameters of steroid sulfatase were determined in the four cell types and were found to be very similar, as were the rates of hydrolysis. Sulfatase activity was linear with incubation time for at least 2 h and with cell number up to 3.2 X 10(6) cells/mL. The apparent pH optimum of steroid sulfatase, determined by the use of cell sonicates and estrone sulfate as the substrate, was between 6.0 and 7.5. The apparent Km values of steroid sulfatase for estrone sulfate in both squamous vaginal carcinoma cells and ovarian carcinoma cells were both 5 microM, and those for dehydroepiandrosterone sulfate in squamous vaginal carcinoma cells and endometrial adenocarcinoma cells were 6 and 4 microM, respectively. The optimal temperature of steroid sulfatase in squamous vaginal carcinoma cells was 50 C; at this temperature, enzymatic activity was more than twice that at 37 C. The steroid sulfatase pathway that is operative in carcinoma cells in vitro to produce free steroids from steroid sulfate precursors also may serve to produce free steroids in vaginal, endometrial, and ovarian carcinomas in vivo and, perhaps, maintain and stimulate tumor growth.
分别研究了硫酸雌酮和硫酸脱氢表雄酮在源自女性下生殖道四种不同恶性肿瘤（即鳞状细胞阴道癌、卵巢癌和两种子宫内膜腺癌）的细胞中酶解生成雌酮和脱氢异雄酮的过程。这些细胞具有水解这两种甾体硫酸酯共轭物的能力。硫酸雌酮作为底物比硫酸脱氢表雄酮更有效，因为由硫酸雌酮生成的产物量大约是由硫酸脱氢表雄酮生成产物量的3倍。测定了这四种细胞类型中甾体硫酸酯酶的一些动力学参数，发现它们非常相似，水解速率也是如此。硫酸酯酶活性与孵育时间至少2小时呈线性关系，与细胞数量在高达3.2×10⁶个细胞/毫升时呈线性关系。通过使用细胞超声裂解物和硫酸雌酮作为底物测定的甾体硫酸酯酶的表观最适pH在6.0至7.5之间。鳞状阴道癌细胞和卵巢癌细胞中甾体硫酸酯酶对硫酸雌酮的表观Km值均为5微摩尔，鳞状阴道癌细胞和子宫内膜腺癌细胞中甾体硫酸酯酶对硫酸脱氢表雄酮的表观Km值分别为6微摩尔和4微摩尔。鳞状阴道癌细胞中甾体硫酸酯酶的最适温度为50℃；在此温度下，酶活性是37℃时的两倍多。在体外癌细胞中起作用的从甾体硫酸酯前体产生游离甾体的甾体硫酸酯酶途径在体内的阴道、子宫内膜和卵巢癌中也可能用于产生游离甾体，并且可能维持和刺激肿瘤生长。
