2. 正常並びに病的標的組織系におけるステロイドホルモン受容体とその意義
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i) Brain receptors : Specific progesterone (P) receptors have been demonstrated in estrogen (E) -primed rat hypothalamus and anterior hypophysis, suggesting that P acts upon the brain through its receptors (R). Along with the presence of R for E, androgens (A) and corticoids in the brain, this may validate the hypothesis of the "one to one correspondence" relationship between the steroid hormone and its R.<BR>ii) Chromatin binding : Binding of estradiol (E<SUB>2</SUB>) cytosol R complexes to chromatin prepared from E sensitive (hypothalamus, hypophysis and uterus) and non-sensitive (cerebral cortex and spleen) tissues was examined to elucidate the regulative mechanism of specificity of the E sensitive cells in the brain and hypophysis. Chromatin binding depended roughly upon the amount of the cytosol Rs contained in the cells. The specificity of the target cells seemed also to be regulated at the chromatin level to some extent. In this context it is worthy that E cytosol receptors (ER) obtained from rat hypothalamus and anterior hypophysis were very similar, suggesting possible absence of organ specificity of the ERs in the hypothalamo-hypophysial-uterine system. Differential effects of E in the target tissues may be ascribable to the events after cytosol R.<BR>iii) ER in the target system of primates and hum ans : The concentrations of ER in human uterine cytosols were the endometrium > the cervix > the myometrium >> the tube. ER was isolated by gradient centrifugation from anterior hypophysial cytosols from the Rhesus monkey. Furthermore, on sucrose density gradients of normal anterior hypophysial cytosols obtained from a patient with advanced metastatic breast cancer, there was distinct binding of P and dexamethasone, suggesting the presence of possible Rs for steroid hormones in human central targets.<BR>iv) Applicability of newly synthetic steroids for receptorassay : R5020, R1881 and R2858 were employed for analysis of P-, A-and E Rs, respectively, in human breast cancer, human endometrial cancer, rat pituitary tumors and fetoneonatal rat brain. Decreasing concentrations of ER and PR were found in endometrial cancer with increasing grade of undifferentiation. These synthetic steroids have been found as valuable tools for the receptorassay, basically or clinically.
- 一般社団法人 日本内分泌学会の論文
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- 2. 正常並びに病的標的組織系におけるステロイドホルモン受容体とその意義
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- 特別発言 : エストロゲンとプロゲステロンの相互作用と受容体調節