雌激素受体的免疫内分泌学

The immunoendocrinology of estrophilin.

作者信息

Jensen E V, Greene G L, Closs L E, DeSombre E R

出版信息

Adv Exp Med Biol. 1979;117:1-16. doi: 10.1007/978-1-4757-6589-2_1.

Abstract

Immunoglobulin from the serum of rabbits immunized with highly purified estradiol-receptor complex from calf uterine nuclei has been shown to contain specific antibodies to estrophilin by five criteria. Antibodies to calf nuclear estrophilin cross react with nuclear estradiol-receptor complexes of rat, rabbit and sheep uterus, rat endometrial and pituitary tumor, and MCF-7 human breast cancer cell line. They also react with extranuclear receptor of calf, rat, mouse, rabbit, guinea pig, monkey and sheep uterus, rat mammary, endometrial and pituitary tumor, and human breast cancer. There is no interaction of the antibody with estradiol itself. The nuclear form of estrophilin appears to bind more immunoglobulin molecules than does the cytosol form. The antibodies do not react with either the nuclear or extranuclear dihydrotestosterone-receptor complexes of rat prostate, with the extranuclear progesterone-receptor complexes of rabbit uterus, chick oviduct or rat endometrial tumor, or with rat and mouse alpha-fetoprotein. These findings indicate an immunochemical similarity among estrophilins from several mammalian species, as well as between nuclear and extranuclear forms of the receptor, but not among receptor proteins for different steroid hormones. Immunoglobulin from the serum of a goat immunized with similar antigen shows a considerably higher titer of antibodies to estrophilin. These react with nuclear and extranuclear estradiol-receptor complexes of calf uterus to produce somewhat larger entities than those formed with the rabbit antibody. Unlike the rabbit antibody, interaction with the goat antibody causes a noticeable decrease in estradiol-binding affinity of the extranuclear estrophilin as well as an apparent decrease in the total hormone-binding capacity. Specific antibodies to estrophilin offer promise as valuable reagents for receptor analysis and purification, as well as for the elucidation of many still unresolved questions concerning receptor synthesis, localization and function.

摘要

通过五条标准已证实，用从犊牛子宫核中高度纯化的雌二醇受体复合物免疫的兔血清中的免疫球蛋白含有对雌激素受体的特异性抗体。针对犊牛细胞核雌激素受体的抗体可与大鼠、兔和绵羊子宫的核雌二醇受体复合物、大鼠子宫内膜和垂体肿瘤以及MCF - 7人乳腺癌细胞系发生交叉反应。它们还与犊牛、大鼠、小鼠、兔、豚鼠、猴和绵羊子宫的核外受体、大鼠乳腺、子宫内膜和垂体肿瘤以及人类乳腺癌发生反应。该抗体与雌二醇本身无相互作用。雌激素受体的核形式似乎比胞质形式结合更多的免疫球蛋白分子。这些抗体与大鼠前列腺的核或核外二氢睾酮受体复合物、兔子宫、鸡输卵管或大鼠子宫内膜肿瘤的核外孕酮受体复合物以及大鼠和小鼠甲胎蛋白均无反应。这些发现表明，几种哺乳动物物种的雌激素受体之间以及受体的核形式和核外形式之间存在免疫化学相似性，但不同类固醇激素的受体蛋白之间不存在这种相似性。用类似抗原免疫的山羊血清中的免疫球蛋白显示出对雌激素受体的抗体效价明显更高。这些抗体与犊牛子宫的核和核外雌二醇受体复合物发生反应，产生的复合物比与兔抗体形成的复合物稍大。与兔抗体不同，与山羊抗体的相互作用会导致核外雌激素受体的雌二醇结合亲和力显著降低，以及总激素结合能力明显下降。针对雌激素受体的特异性抗体有望成为受体分析和纯化的有价值试剂，以及用于阐明许多关于受体合成、定位和功能的仍未解决的问题。