Graduate School of Pharmaceutical Sciences, Duquesne University, USA.
Exp Eye Res. 2013 Jul;112:1-9. doi: 10.1016/j.exer.2013.04.002. Epub 2013 Apr 15.
Estrogen is reported to be protective against cataracts in women and animal models. Immunodetection methods have identified the classic estrogen receptors (ER), ERα and ERβ, in human lens epithelial cells and their RNAs have been detected in the rat and human lens. To verify that estrogen binding occurs in the lens, sensitive [(125)I]-17β-estradiol binding analyses were performed on subcellular lens fractions from women (ages 39-78 years). The presence of high affinity estradiol binding sites in the nuclear, cytoplasmic, and membrane fractions indicate the lens is able to respond to estrogens, even up to age 78, although fewer binding sites were detected in the postmenopausal women. Additionally, due to the importance of mouse models in estrogen action and lens research, lenses from intact female mice were also analyzed. Both the C57BL/6 and FVB/N mouse strains also possessed high affinity binding sites in all three lens fractions. Furthermore, transcripts for ERα, ERβ, and G protein-coupled estrogen receptor (GPER; previously called GPR30) that bind estradiol with high affinity were expressed in the human and mouse lenses. These data provide the first evidence of GPER expression in the lens. Its role, functions, and subcellular location are currently unknown, but a G-shift assay in the membrane fractions of human and mouse lenses did not show evidence that estradiol induced classic G protein-coupled receptor activation. All three receptor transcripts were also detected in the lens capsule region isolated from female C57BL/6 mice, which is mainly comprised of epithelial cells. In contrast, only ERα and GPER were expressed in the cortex/nuclear region, which is primarily composed of differentiating and organelle-free fiber cells. No significant differences in specific estradiol binding and receptor RNA expression were observed in the lenses between male and female C57BL/6 mice. These findings indicate that the lens is an estrogen target tissue in both sexes. The identification of GPER, in addition to ERα and ERβ, in the lens also adds to the complexity of possible estrogen responses in the lens. Accordingly, the protective effects of estrogen in women and animals may be mediated by all three estrogen receptors in the lens. In addition, the similarities in binding and receptor RNA expression in the lenses of both species suggest that mice can be used to model estrogen action in the human lens.
雌激素据报道对女性和动物模型的白内障有保护作用。免疫检测方法已在人晶状体上皮细胞中鉴定出经典的雌激素受体（ER），ERα和 ERβ，并且在大鼠和人晶状体中已检测到其 RNA。为了验证雌激素结合发生在晶状体中，对来自女性（年龄 39-78 岁）的亚细胞晶状体部分进行了灵敏的[(125)I]-17β-雌二醇结合分析。核、细胞质和膜部分中高亲和力雌二醇结合位点的存在表明，即使在 78 岁时，晶状体也能够对雌激素产生反应，尽管在绝经后女性中检测到的结合位点较少。此外，由于在雌激素作用和晶状体研究中小鼠模型的重要性，还分析了完整雌性小鼠的晶状体。C57BL/6 和 FVB/N 两种小鼠品系在所有三种晶状体部分也都具有高亲和力结合位点。此外，人晶状体和小鼠晶状体中还表达了与雌二醇具有高亲和力结合的 ERα、ERβ 和 G 蛋白偶联雌激素受体（GPER；以前称为 GPR30）的转录本。这些数据提供了 GPER 在晶状体中表达的第一个证据。其作用、功能和亚细胞定位目前尚不清楚，但在人晶状体和小鼠晶状体的膜部分中的 G 移位测定中没有显示出雌二醇诱导经典 G 蛋白偶联受体激活的证据。三种受体转录本也在从雌性 C57BL/6 小鼠分离的晶状体囊区中被检测到，该区域主要由上皮细胞组成。相比之下，仅在主要由分化和细胞器自由纤维细胞组成的皮质/核区中表达 ERα 和 GPER。在 C57BL/6 雄性和雌性小鼠的晶状体中，没有观察到雌二醇结合和受体 RNA 表达的特异性差异。这些发现表明，在两性中晶状体都是雌激素的靶组织。除 ERα 和 ERβ 外，在晶状体中鉴定出的 GPER 也增加了晶状体中可能的雌激素反应的复杂性。因此，雌激素对女性和动物的保护作用可能是由晶状体中的三种雌激素受体介导的。此外，两种物种晶状体中结合和受体 RNA 表达的相似性表明，小鼠可用于模拟人晶状体中的雌激素作用。
