Buchanan D L, Kurita T, Taylor J A, Lubahn D B, Cunha G R, Cooke P S
Department of Veterinary Biosciences, University of Illinois, Urbana 61802, USA.
Endocrinology. 1998 Oct;139(10):4345-52. doi: 10.1210/endo.139.10.6241.
Estradiol 17-beta (E2) induces epithelial proliferation, stratification, and cornification in vaginal epithelium. Our aim was to determine the respective roles of epithelial and stromal estrogen receptor-alpha (ER alpha) in these E2-induced events. Vaginal epithelium (E) and stroma (S) from adult ER alpha knockout (ko) and wild-type (wt) neonatal Balb/c mice were enzymatically separated and used to produce four types of tissue recombinants in which epithelium, stroma, or both lack functional ER alpha. Tissue recombinants were grafted into female nude mice, which were subsequently ovariectomized and treated with oil or E2. In response to E2 treatment, grafts prepared with wt-S (wt-S + wt-E and wt-S + ko-E) showed similar large increases in epithelial labeling index, indicating that E2 stimulated epithelial proliferation despite a lack of epithelial ER alpha in wt-S + ko-E tissue recombinants. Conversely, in tissue recombinants prepared with ko-S (ko-S + wt-E and ko-S + ko-E), epithelial labeling index remained at baseline levels after E2 or oil treatment, even though epithelial ER alpha were detected in ko-S + wt-E grafts. Epithelial cornification was present in wt-S + wt-E grafts from E2-treated hosts, whereas epithelium in all other tissue recombinants failed to cornify. Grafts composed of wt-S + wt-E from E2-treated hosts had highly stratified epithelium, whereas epithelial thickness was reduced almost 60% in wt-S + ko-E tissue recombinants grown in E2-treated hosts and was atrophic in all other tissue recombinants. In addition, cytokeratin 10, a marker of epithelial differentiation, was strongly expressed in wt-S + wt-E tissue recombinants grown in E2-treated hosts but was markedly reduced or absent in all other tissue recombinants. These results indicate that E2-induced vaginal epithelial proliferation is mediated indirectly through stromal ER alpha, consistent with our recent findings in uterus. Conversely, both epithelial and stromal ER alpha are required for E2-induced cornification and normal epithelial stratification. These are the first known functions attributed to epithelial ER alpha in vivo and the first time any epithelial response to E2 has been shown to involve both stromal and epithelial ER alpha.
17-β-雌二醇（E2）可诱导阴道上皮细胞增殖、分层和角质化。我们的目的是确定上皮细胞和基质雌激素受体α（ERα）在这些E2诱导事件中的各自作用。从成年ERα基因敲除（ko）和野生型（wt）新生Balb/c小鼠中酶解分离出阴道上皮（E）和基质（S），并用于制备四种类型的组织重组体，其中上皮、基质或两者均缺乏功能性ERα。将组织重组体移植到雌性裸鼠体内，随后对其进行卵巢切除并用油或E2处理。响应E2处理，用wt-S制备的移植物（wt-S + wt-E和wt-S + ko-E）显示上皮标记指数有类似的大幅增加，表明尽管在wt-S + ko-E组织重组体中上皮缺乏ERα，但E2仍刺激上皮细胞增殖。相反，在用ko-S制备的组织重组体（ko-S + wt-E和ko-S + ko-E）中，即使在ko-S + wt-E移植物中检测到上皮ERα，E2或油处理后上皮标记指数仍保持在基线水平。E2处理宿主的wt-S + wt-E移植物中存在上皮角质化，而所有其他组织重组体中的上皮均未角质化。E2处理宿主的由wt-S + wt-E组成的移植物具有高度分层的上皮，而在E2处理宿主中生长的wt-S + ko-E组织重组体中上皮厚度几乎减少了60%，并且在所有其他组织重组体中均萎缩。此外，细胞角蛋白10是上皮分化的标志物，在E2处理宿主中生长的wt-S + wt-E组织重组体中强烈表达，但在所有其他组织重组体中明显减少或缺失。这些结果表明，E2诱导的阴道上皮细胞增殖是通过基质ERα间接介导的，这与我们最近在子宫中的发现一致。相反，E2诱导的角质化和正常上皮分层需要上皮和基质ERα。这些是体内归因于上皮ERα的首批已知功能，也是首次证明任何上皮对E2的反应都涉及基质和上皮ERα。
