Biological and clinical aspects of estrogen receptor-related evidences

雌激素受体相关证据的生物学和临床方面

• 批准号: 01480390
• 负责人: TAMAYA Teruhiko
• 金额: $ 3.97万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480390/
• 关键词: Estrugen Action; Estradiol Receptor; Estriol Receptor; Biological Aspect; Clinical Aspect

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

雌激素对女性生殖道、神经、血管和肌肉系统发挥生物学作用，促进细胞增殖和分化。雌激素可分为两类：具有强增殖活性的雌二醇（E_2）和具有弱增殖活性和抗E_2活性的雌三醇（E_3）。前者是子宫内膜癌的风险，但后者不是。此外，雌激素的作用还与核受体的相互作用有关。本研究的目的是为了澄清的差异。E_2和E_3的分子生物学研究表明，E_2和E_3受体分别位于兔子宫和人子宫中。E_2能刺激家兔子宫E_2R和E_3R的合成。E_2R和E_3R分布于家兔的脑、肝、肾和血管，垂体E_3R含量高于脑和子宫。抗雌激素，如他莫昔芬和cl ...更多信息 Omiphene对E_3R的亲和力是对E_2R的两倍。提示E_3对垂体功能有较强的调节作用，抗雌激素作用与E_3R可能存在交互作用。醋酸甲羟孕酮和达那唑可通过降低子宫E_2R和E_3R来抑制雌激素诱导的兔子宫生长。家兔心血管系统和肌肉系统的E_2R和E_3R在雌雄间存在二态性。E_3 R在人体内的含量由高到低依次为阴道、子宫体、宫颈。正常子宫内膜中E_2R的含量是E_3R的2倍，而子宫内膜癌中E_3R的含量是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抗肿瘤药物，在体外培养的人子宫内膜成纤维细胞中，E_2可能通过相互作用发挥作用。E_3对细胞膜有刺激作用，刺激肌醇磷脂和前列腺素系统，而E_3对细胞膜无刺激作用，一般有两种结合位点，即与细胞增殖有关的Ⅰ型和与细胞分化有关的Ⅱ型。这些类型的位点存在于人单核巨噬细胞中，其中II型位点比I型位点多得多。雌激素II型位点可能与细胞因子的产生有关。达那唑具有雄激素作用，减少单核-巨噬细胞的典型位点，同时减少细胞因子的产生。雌、孕激素在生理剂量下可发挥刺激作用，而在药理剂量下作用与达那唑相似。提示雌、雄激素对单核-巨噬细胞的影响可能与雌、雄激素的免疫二型性有关。少

项目成果

Teruhiko Tamaya,et al.: "Rationale for frequency and dose of administration in gestrinone therapy for pelvic endometriosis in the experimental model of rabbit uterus" Gen.Pharmac.22. 505-510 (1991)

Teruhiko Tamaya 等人：“兔子宫实验模型中孕三烯酮治疗盆腔子宫内膜异位症的给药频率和剂量的基本原理”Gen.Pharmac.22。

A. A. Khan, A., Tamaya, T.: "Possible mechanism for preterm labor associated with bacterial infection II : Enhancement of endotoxin stimulated phosphoinositide metabolism by sex steroids in human endometrial fibroblasts" Res. Comm. Pathol. Pharmacology. 6

A. A. Khan, A.，Tamaya, T.：“与细菌感染相关的早产的可能机制 II：在人子宫内膜成纤维细胞中通过性类固醇增强内毒素刺激的磷酸肌醇代谢”Res。

Mori, H., Nakagawa, M., Itoh, N., Wada, K., Tamaya, T.: "Danazol suppresses the productions of interleukin-1 beta and tumor necrosis factor by human monocytes." Am. J. Reproduct. Immunol.24. 45-50 (1990)

Mori, H.、Nakakawa, M.、Itoh, N.、Wada, K.、Tamaya, T.：“达那唑抑制人单核细胞产生白细胞介素 1 β 和肿瘤坏死因子。”

Tamaya, T., Wada, K., Imai, A., Mori, H., Ban, H.: "Rationale for frequency and dose of administration in gestrinone therapy for pelvic endometriosis in the experimental model of rabbit uterus." Gen. Pharmac.22. 505-510 (1991)

Tamaya, T.、Wada, K.、Imai, A.、Mori, H.、Ban, H.：“兔子宫实验模型中孕三烯酮治疗盆腔子宫内膜异位症的给药频率和剂量的基本原理。”

H.Mori et.al.: "Danazol Suppresses the Productions of Interleukinー1β and Tumor Necrosis Factor by Human Monocytes" Am.J.Reproductive Immunology. 24. 45-50 (1990)

H.Mori 等人：“达那唑抑制人单核细胞产生白细胞介素 1β 和肿瘤坏死因子”Am.J.ReproductiveImmunology 24. 45-50 (1990)。