Section of Oncology, Institute of Medicine, University of Bergen, Norway.
Steroids. 2011 Jul;76(8):786-91. doi: 10.1016/j.steroids.2011.02.040. Epub 2011 Mar 31.
The contribution of local synthesis versus circulatory delivery of normal breast as well as breast cancer tissue estrogens has remained a controversial area for decades. Novel data on tissue estrogen levels confirm a positive normal breast tissue to plasma concentration gradient for estrone, and to a smaller extent estradiol. Remarkably, this gradient is similar for pre- and post-menopausal women. Together with pharmacokinetic data on estrogen disposition, these findings suggest plasma and breast tissue estrogens to rapidly equilibrate, with circulating estrogens being a major contributor to breast tissue estrone levels. A likely explanation to the concentration gradient could be the fact that non-polar estrogens easily dissolve into tissue fat compartments as compared to plasma. While intratumor estrone levels are low as compared to benign tissue concentrations, intratumor estradiol is elevated in ER+ tumors. The correlation between intratumor estradiol levels and expression levels of dehydrogenases reducing estrone into estradiol but also intratumor ER concentrations are consistent with intratumor estrogen activation but also a scavenger effect of the ER.
局部合成与循环输送正常乳腺以及乳腺癌组织雌激素的贡献在几十年来一直是一个有争议的领域。关于组织雌激素水平的新数据证实，雌酮在正常乳腺组织与血浆之间存在正的浓度梯度，而雌二醇的梯度则较小。值得注意的是，这种梯度在绝经前和绝经后妇女中相似。结合关于雌激素处置的药代动力学数据，这些发现表明血浆和乳腺组织中的雌激素能够迅速达到平衡，循环中的雌激素是乳腺组织中雌酮水平的主要贡献者。这种浓度梯度的一个可能解释是，与血浆相比，非极性雌激素很容易溶解到组织脂肪隔室中。虽然与良性组织浓度相比，肿瘤内的雌酮水平较低，但 ER+肿瘤中的肿瘤内雌二醇水平升高。肿瘤内雌二醇水平与将雌酮还原为雌二醇的脱氢酶的表达水平之间以及肿瘤内 ER 浓度之间的相关性与肿瘤内雌激素的激活以及 ER 的清除效应一致。
