Biological and clinical aspects of estrogen receptor-related evidences

雌激素对女性生殖道以及神经、血管和肌肉系统发挥生物学作用，有助于细胞的增殖和分化。雌激素分为促增殖活性强的17β雌二醇(E_2)和低促增殖活性和抗E_2活性的雌三醇(E_3)两组。前者对子宫内膜癌有风险，而后者则没有。此外，雌激素的作用与其与核受体的相互作用有关。这项研究旨在澄清两者之间的区别。E_2特异性受体(E_2R)和E_3特异性受体(E_3R)分别位于兔子宫和人子宫中。在兔体内，E_2能刺激E_2R和E_3R的合成。E_2R和E_3R在兔脑、肝、肾和血管中均有分布，脑垂体中E_3R的含量高于脑和子宫。抗雌激素，如他莫昔芬和CL…更多的奥米芬对E_3R的亲和力是对E_2R亲和力的两倍。提示E_3对垂体功能具有潜在的调节作用，抗雌激素作用可能与E_3R相互作用。醋酸美托孕酮和达那唑可抑制雌激素诱导的兔子宫生长，降低子宫E_2R和E_3R。雌雄动物心血管和肌肉系统存在E_2R和E_3R的二型性。提示这种二态现象与心血管疾病的发生和肌肉形态表型的性别差异有关。在人体中，E_3R含量由高到低依次为阴道、体和宫颈。正常子宫内膜中E_2R的含量是E_3R的两倍，而子宫内膜癌的E_3R是E_2R的4~6倍。提示E_3可能对阴道有作用，E_3相关化合物可能成为一种抗肿瘤药物。在培养的人子宫内膜成纤维细胞中，E_2可通过相互作用发挥作用。雌激素有两种结合部位，即与细胞增殖有关的I型结合部位和与细胞分化有关的II型结合部位。这些类型的位点存在于人单核巨噬细胞中，其中类型II的位点比类型I的位点多得多。Estorgen II型位点可能与细胞因子的产生有关。在雄激素作用下，丹那唑减少了单核巨噬细胞的类型，同时减少了细胞因子的产生。雌激素和孕酮在生理剂量下均能发挥刺激作用，但在药理剂量上与达那唑相似。提示雌雄激素对单核巨噬细胞的作用可能与雌雄激素的免疫二型性有关。较少

Estrogen exerts its biological effects on female reproductive tract and nervous, vascular and muscular systems, which contribute to proliferation and differentiation for cells. Estrogen is segregated into 2 groups such as estradiol-17 beta(E_2)With potent proliferative activity and estriol(E_3)with less proliferative activity and anti-E_2 activity. The former is risky for endometrial cancer, but the latter is not. In addition, estrogeri action is related to the interaction to nuclear receptor. This study is designed to clarify the difference of. E_2 and E_3 from the molecularbiological aspects.E_2-specific receptor(E_2R)and E_3-specific receptor(E_3R)are individually located in the rabbit uterus and the human uterus. In rabbits, E_2 can stimulate the synthesis Qf both E_2R and E_3R in theu terus. E_2R and E_3R are localized in the brain, liver, kidney and vessel of the rabbit, and pituitary E_3R content is more than ttiat of the brain and uterus. Anti-estrogens such as tamoxifen and cl … More omiphene have twice more affinity to E_3R than to E_2R. It is suggested that E_3 is relatively potential for pituitary function and effects of anti-estrogen are potentially interacted to E_3R.Medroxyprogesterone acetate and danazol can exert the inhibitory effect of estrogen-induced uterine growth, decreasing uterine E_2R and E_3R, in the rabbit. It rabbits, dimorphism of E_2R and E_3R is found in cardiovascular and muscular systems among female and male. It is suggested that this dimorphism is related to the male and female difference of the occurrence of cardiovascular diseases and the phenotype of muscular configuration.In the human subjects, the E_3R content is found to be in the decreasing order of vagina, corpus and cervix. Normal uterine endometrium contains E_2R twice more than E_3R, but uterine endometrial cancer E_3R 4 to 6 times more than E_2R. It is suggested that E_3 is likely to demonstrate its effects on vagina, and that E_3-related compound possibly becomes an anti-tumor agent.In human cultured endometrial fibroblasts, E_2 can exert its effect with the interaction. of plasma membrane, stimulating inositol phospholipid and prostaglandin systems, but E_3 does not.Generally, estrogen has 2 types of binding sites such as type I related to cell proliferation and type II related to cell differentiation. Those types of sites are present in human monocytemacrophage, in which type II sites are contained much more than are type I sites. Estorgen type II sites are possibly related to the production of cytokines. Danazol with an androgen effects, decreases the typell sites of monocute-macrophage, concomitantly with decreased cytokine production. Estrogen and progesterone can exert the stimulatory effect in the physiological dose but the effects similar to danazol in the pharmacological dose. It is suggested that immunological dimorphism of female and male partly contributes to effects of estrogen or androgen on the monocyte-macrophage. Less