Hughes A, Larson S M, Hanson R N, DeSombre E R
Ben May Institute for Cancer Research, University of Chicago, IL 60637, USA.
Steroids. 1997 Feb;62(2):244-52. doi: 10.1016/s0039-128x(96)00206-1.
This study compares the specific uptake and retention of the Z and E isomers of 17 alpha-iodovinyl-11 beta-methoxyestradiol (IVME2) in estrogen target tissues in immature female rats following intraperitoneal injection. Estrogen receptor binding studies in vitro showed that the Z-IVME2 had greater affinity than the E-IVME2, but our initial in vivo data, comparing 125I-labeled E- or Z-IVME2 in separate studies showed no difference between the two isomers in either uptake or retention. These results were confirmed when the two isomers, labeled either with 123I or 125I, were injected simultaneously, allowing direct comparison of uptake and retention patterns in the same animal. Analysis of the nature of the radioiodinated estrogens in estrogen target tissues showed that at all time points, the estrogen target tissues contained mainly the E isomer, even at short times after injection of Z isomer. Although the Z-IVME2 was reasonably stable in the injectant, analysis of a peritoneal lavage soon after intraperitoneal injection of Z-[125I]-IVME2 showed that mainly the E isomer was present, suggesting that the conversion occurred prior to uptake by the tissues. In vitro studies with intraperitoneal fluid and serum showed that denaturing by heating at 65 degrees C substantially reduced their ability to affect the conversion of Z to E isomer, suggesting a possible enzymatic conversion.
本研究比较了腹腔注射后未成熟雌性大鼠雌激素靶组织中17α-碘乙烯基-11β-甲氧基雌二醇（IVME2）的Z型和E型异构体的特异性摄取和滞留情况。体外雌激素受体结合研究表明，Z-IVME2比E-IVME2具有更高的亲和力，但我们最初的体内数据，在单独研究中比较125I标记的E-IVME2或Z-IVME2，显示两种异构体在摄取或滞留方面没有差异。当同时注射用123I或125I标记的两种异构体时，这些结果得到了证实，从而可以直接比较同一动物中的摄取和滞留模式。对雌激素靶组织中放射性碘化雌激素的性质分析表明，在所有时间点，雌激素靶组织主要含有E型异构体，即使在注射Z型异构体后的短时间内也是如此。尽管Z-IVME2在注射剂中相当稳定，但腹腔注射Z-[125I]-IVME2后不久对腹腔灌洗液的分析表明，主要存在的是E型异构体，这表明这种转化发生在组织摄取之前。用腹腔液和血清进行的体外研究表明，在65℃加热变性会大大降低它们影响Z型向E型异构体转化的能力，这表明可能存在酶促转化。
