| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1991: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1990: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1989: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Research Abstract |
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
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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
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