Wittliff J L, Mehta R G, Boyd P A, Goral J E
J Toxicol Environ Health Suppl. 1976;1:231-56.
Differentiation and development of the mammary gland are influenced by estrogens, glucocorticoids, and progesterone. Specific binding sites for each of these classes of steroid hormones have been characterized in vivo and in cell-free preparations of lactating mammary gland of the rat. These properties were compared with those of steroid-binding proteins in the R3230AC and dimethylbenz[a]anthracene-induced mammary tumors of the rat and of human breast carcinomas. The binding components that were protein in nature were more concentrated in tissue from lactating than from virgin or pregnant rats. The steroid-binding capacities of mammary tumors were highly variable. Using a dextran-coated charcoal procedure, the rate constants of 3H-ligand association with specific binding sites were temperature dependent. Ligand specificity indicated that [3H]estradoil-17beta(3H-E) binding was inhibited only by estrogens, whereas [3H]triamcinolone acetonide (3 H-TA) was blocked by glucocorticoid/s and progesterone. Likewise, [3H]progesterone (3H-P) binding was inhibited by progestins and certain glucocorticoids. Incubation of minced mammary gland with 3H-steroid in the presence and absence of unlabeled competitor demonstrated specific binding sites in cytoplasm that were translocated to nuclei in a tempreature-dependent fashion. Using a steroid-exchange procedure both DEX and TA inhibited 3H-P binding to exchangeable sites that were loaded previously with unlabeled progesterone. These data suggest that certain glucocorticoid and progesterone binding sites were translocated simultaneously to nuclei. Administration in vivo of either 3H-E or 3H-TA indicated binding in cytoplasm and subsequent translocation to nuclei.
乳腺的分化和发育受雌激素、糖皮质激素和孕酮的影响。已在大鼠泌乳期乳腺的体内和无细胞制剂中鉴定出这些类固醇激素各自的特异性结合位点。将这些特性与大鼠R3230AC和二甲基苯并[a]蒽诱导的乳腺肿瘤以及人类乳腺癌中的类固醇结合蛋白特性进行了比较。本质上为蛋白质的结合成分在泌乳大鼠组织中的浓度高于未生育或怀孕大鼠。乳腺肿瘤的类固醇结合能力高度可变。使用葡聚糖包被活性炭法，3H配体与特异性结合位点的缔合速率常数与温度有关。配体特异性表明，[3H]雌二醇-17β（3H-E）结合仅受雌激素抑制，而[3H]曲安奈德（3H-TA）则被糖皮质激素和孕酮阻断。同样，[3H]孕酮（3H-P）结合受孕激素和某些糖皮质激素抑制。在有无未标记竞争剂存在的情况下，用3H-类固醇孵育切碎的乳腺，结果表明细胞质中的特异性结合位点以温度依赖的方式转移到细胞核。使用类固醇交换程序，地塞米松（DEX）和曲安奈德（TA）均抑制3H-P与先前加载未标记孕酮的可交换位点的结合。这些数据表明，某些糖皮质激素和孕酮结合位点同时转移到细胞核。体内给予3H-E或3H-TA表明在细胞质中结合并随后转移到细胞核。
