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T Shimura

Publications and source records attributed to T Shimura.

143 records · Page 8Linked to original sources
PubMed1977

Contribution of functional groups of 19-nor-progestogens to binding to progesterone and estradiol-17beta receptors in rabbit uterus.

The structural elements of 19-norprogestogens which may be essential for binding to progesterone and estradiol-17beta(E2) receptors were investigated in the rabbit uterine cytosol. The kinetic study showed that 19-nor-progestogens are competitive inhibitors of progesterone-receptor (8S) binding and E2-receptor binding. The affinities of steroids for the progesterone receptor were as follows: norethindrone (Ki of 2.3 X 10(-9)M) greater than 5alpha-dihydronorethindrone greater than norethindrone acetate greater than lynestrenol greater than 17alpha-ethynyl-estra-4-ene-3beta, 17beta-diol greater than ethynodiol diacetate (Ki of 1.3 X 10(-7) M). The affinities of steroids for the E2 receptor were as follows: ethynodiol diacetate (Ki of 1.3 X 10(-7)M) greater than 17alpha-ethynyl-estra-4-ene-3beta, 17beta-diol greater than norethindrone acetate greater than norethindrone greater than 5alpha-dihydronorethindrone greater than lynestrenol (Ki of 8.4 X 10(-7)M). The results indicate that 3-ketone and 17beta-hydroxyl groups, and the plane of ring A/B of 19-norprogestogen are important for binding to the progesterone receptor. The affinities of 19-nor-progestogens for the E2 receptor were very weak. Their affinities for the E2 receptor increased with addition of acetate or hydroxyl groups at the 3beta and 17beta positions, and were decreased by the elimination of a 3 oxygen function or the reduction of ring A.

Animals↗
PubMed1977

Progesterone receptor in human endometrium of leiomyoma uteri.

This study was designed to examine whether 8S protein as progesterone receptor exists in the human endometrium which has been primed with estrogen. The kinetic study showed that 8S-progesterone binding was specific with Kd of 2.0 X 10(-9) M. 5S-progesterone binding was inhibited competitively by cortisol. The study of ligand specificity also showed that progesterone and its related steroids had much stronger affinity for 8S component than for 5S component. Therefore, 5S protein may be CBG. Progesterone-8S protein binding was easily dissociated during the 5-20% sucrose gradient centrifugation, but such a protein from which progesterone had been dissociated could be sedimented at 8S region. Glycerol could stabilize progesterone-8S protein binding. These results indicate the existence of 8S protein as a progesterone receptor under the low salt medium in the estrogen primed human endometrium.

Endometrium↗
PubMed1975

[Studies on progesterone receptor in rabbit uterine cytosol -- nuclear translocation and chromatin binding-- (author's transl)].

Estrogen priming increases uterine 8S macromolecule which binds progesterone specifically. Progesterone-8S complex in the cytoplasm enters into nucleus and is bound to chromatin finally. In this paper, the mode of nuclear translocation of steroid in exchange assay of receptor introduced by Anderson et al., and the mode of binding to chromatin were studied on the progesterone-receptor complex in the uterus of estrogen primed female rabbit. 1. After intravenous administration of 200 mug progesterone into the estrogen primed immature rabbit, uterine nuclei were prepared by the method in Table 1. These nuclei were incubated with 3H-progesterone and cold steroids at 4 degrees C for 30 minutes, and then washed with buffer A. The radioactivity of the nuclei was counted. This experiment was performed at 4 degrees C because progesterone receptor and chromatin were observed to be degraded at 37 degrees C for 20 minutes. The effect of cold steroids in vitro on the incorporation of 3H-progesterone into the uterine nuclei of rabbit pretreated with progesterone was found to be similar to their effect on progesterone-receptor binding in cytosol or chromatin (Fig. 1). 2. The effect of cold steroids on 3H-progesterone-receptor-chromatin triplex (Table 2 and Fig. 2) was examined. Once 3H-progesterone-receptor-chromatin triplex was formed, it was difficult to exchange 3H-progesterone to other steroids at 4 degrees C. These results (1 & 2) indicate that progesterone-receptor complex enters into nucleus and is bound to chromatin. Exchange of steroid may occur in the nuclear progesterone-receptor complex, which is free from the binding with chromatin. And thus exchange assay cannot represent quantitative data on receptor content. 3. 3H-progesterone-8S or 5S complexes were obtained by 5 approximately 20% sucrose linear gradient centrifugation (Fig. 3). The same molar concentration of these complexes from estrogen primed or castrated rabbit uterus were incubated with primed uterine chromatin for 30 minutes. Then the chromatin was washed with buffer A and the radioactivity was counted. It was shown in Fig. 4 that 3H-progesterone-8S complex was bound to chromatin much more tightly than 3H-progesterone 5-S complex in preparations obtained from both castrated or primed uterine cytosols. All these results indicate that 8S may be the biologically active form of the receptor. 4.3H-progesterone uptake into uterine nuclei was observed in very limited amount following the injection into uterine artery. The radioactivity in nuclei decreased easily by washing with buffer A as in Fig. 5. The small amount of residual radioactivity after washing, that is, very limited number of binding sites with high affinity is considered to be indicative of biologically active binding.

Animals↗
PubMedDate not supplied

Brain transfer of a new neuromodulating ACTH analog, ebiratide, in rats.

The transfer of ebiratide into the brain was examined in rats. Its brain levels after intravenous administration (2-20 mg/kg), determined by radioimmunoassay, peaked at 5 min and declined almost in parallel with the plasma levels. Brain/plasma ratios (B/P) were constantly about 0.05 ml/g at all doses. Brain distribution study at 5 min after 125I-ebiratide at an effective dose (0.4 microgram/kg) revealed that unchanged ebiratide had larger B/P than the metabolites and region selectivity. The combined use with unlabeled ebiratide resulted in marked decreases in B/P, particularly in the hippocampus, suggesting a specific uptake of this peptide.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Effects of iso and xeno fetal liver fragments transplantation on acute and chronic liver failure in rats.

Isogeneic (rat) and xenogeneic (swine) fetal liver fragments (FLF) transplantation into the omentum was performed for D-galactosamine (D-Gal)-induced acute and carbon tetrachloride (CCl4)-induced chronic hepatic failure in rats. The recipients that had iso or xeno FLF showed higher survival rates than the nontransplanted controls on a lethal dose (2.6 g/kg body weight) of D-Gal (survival rates: Iso 70%, Xeno 80%, and control 9.1%). On a sublethal dose (1.0 or 1.2 g/kg) of D-Gal, iso, or xeno FLF caused marked improvement of the values of GPT, GOT, and total bilirubin (T.Bil); at 72 h after D-Gal injection they went significantly lower than those of controls (Iso vs. control; p < 0.01, Xeno vs. control; p < 0.05). Histological examination of the livers revealed severe damage in controls, however, only a slight damage was found in iso or xeno FLF transplanted rats. Iso grafts were fairly well preserved in the omentum at 72 h posttransplants, however, xeno graft had almost changed into a necrotic tissue. CCl4 was administered subcutaneously for 14 wk to induce chronic hepatic failure and then iso FLF were transplanted 3 days after the last CCl4 injection. Iso FLF transplanted rats showed higher improvement of GPT and GOT values at 12 days posttransplants compared with controls (GPT p < 0.01, GOT p < 0.05), although histological improvement was not so remarkable in both group. Iso grafts formed nodules with many hepatocytes in the omentum 12 days posttransplant. The results indicate that iso or xeno FLF transplantation could be an alternative approach for incurable liver insufficiencies.

Animals↗