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  • Author: Yoshito Ohba x
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Tohru Yashiro, Yoshito Ohba, Hitomi Murakami, Takao Obara, Toshio Tsushima, Yoshihide Fujimoto, Kazuo Shizume and Kunihiko Ito


The presence of IGF-I receptors was demonstrated in normal and neoplastic tissues of human thyroid. Binding of [125I]IGF-I to thyroid membranes was dependent on time and temperature of incubation, and maximal binding was achieved at 4°C and 18 h of incubation. [125I] IGF-I binding was dose-dependently displaced by unlabelled IGF-I; half-maximal inhibition occurred at concentrations of 10–20 μg/l. IGF-II and insulin had relative potencies of 5 and 1% compared with IGF-I. Scatchard analysis of binding data revealed a single class of IGF-I receptors with high affinity (Ka: 1.2–8.6 × 109 1/mol) in normal thyroid tissues. Affinity cross-linking and autoradiography demonstrated the type I IGF receptors. Specific binding of [125I] IGF-I in thyroid cancer tissues (9.69 ± 2.07% per 200 μg protein; mean ± sem, N = 8) was significantly (p <0.05) higher than that in the surrounding normal tissues (3.03 ± 0.35%, N = 8). In contrast, there was no difference in the binding between adenoma tissues (4.19 ± 0.53%, N = 5) and the adjacent normal tissues (2.94 ± 0.24%, N = 5). The higher IGF-I binding in cancer tissues was due to an increase in the binding capacity without any change in the affinity. The presence of IGF-I receptors suggests a possible role of IGF-I and its receptors in the growth of thyroid cancer cells.

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Osamu Isozaki, Toshio Tsushima, Kanji Sato, Motoyasu Saji, Yoshito Ohba, Naoya Emoto, Yuji Sato and Kauzo Shizume

Abstract. A 54 year old man with markedly elevated serum T3, but without an apparent thyroid disease, was found to have a specific antibody to T3. His serum thyroxine, TBG and TSH were in normal range, but T3-RSU was markedly low. Antibodies to thyroglobulin and microsome were negative. He was judged euthyroid because of a normal basal metabolic rate and a normal thyroidal 123I uptake which was suppressed by T3 adminnistration. When serum was extracted with ethanol prior to assay, serum T3 was found to be in the upper border of normal range. Several experiments revealed the presence of an antibody to T3 in his serum with an affinity constant of 3.3 × 109 m −1. The binding capacity of the antibody was 7.6 ng/mg of IgG. The binding of [125I]T3 was almost specific to T3, and potencies of T4 and fT3 in displacing [125I]T3 binding were only 1.0 and 0.3%, respectively, of that of T3. The antibody contained both kappa and lambda chains and was therefore polyclonal.

The T3 metabolic clearance rate, which was determined by disappearance of injected [125I]T3 from serum, was lower in this patient (7.44 I/day) than in normal. The T3-production rate was decreased to 14.9 μg/day, and serum free T3 concentration as well as urinary T3 excretion rate were also reduced. Since both serum total and free T4 concentrations were normal, the supply of T4 to peripheral tissues would be sufficient to keep this patient in a euthyroid state in spite of the anti-T3 antibody.

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Motoyasu Saji, Osamu Isozaki, Toshio Tsushima, Mariko Arai, Megumi Miyakawa, Yoshito Ohba, Yumi Tsuchiya, Tomohide Sano and Kazuo Shizume

Abstract. The effect of iodide on growth of rat thyroid cells (FRTL-5) was studied. TSH-stimulated cell growth was inhibited by iodide in a concentration-dependent manner, and an effect of iodide was detected at 10−6 mol/l. KClO4 or 1-methylimidazole-2-thiol blocked the effect of iodide, suggesting that iodide uptake and its organification are required to produce the inhibitory effect of iodide on cell growth. Iodide not only decreased TSH-stimulated cAMP production in FRTL-5 cells but also cell growth induced by cAMP. These observations suggest that iodide inhibits TSH-stimulated growth of the cells by attenuating cAMP production and also by acting on the step(s) distal to cAMP generation. The inhibitory effect of iodide was also seen in growth stimulated by insulin, insulin-like growth factor-I or 12-O-tetradecanoyl phorbol 13-acetate, suggesting multiple sites of action of iodide in the process of growth of FRTL-5 cells.

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Naoya Emoto, Toshio Tsushima, Kazuo Shizume, Toshiaki Tanaka, Motoyasu Saji, Yoshito Ohba, Kae Wakai, Mariko Arai and Eiji Ohmura

Abstract. Nb2 cell is a rat lymphoma cell line that responds to lactogens such as prolactin and human growth hormone (hGH) with an increased rate of proliferation. We explored the relationship between the biochemical events induced by hGH and its derivatives and their receptor binding activities. hGH stimulated RNA, DNA and protein synthesis of Nb2 cells as a function of time. Stimulation of RNA and protein was maximal at 2–3 h and 12 h, respectively, after the addition of hGH. DNA synthesis, measured by the rate of [3H]thymidine incorporation, reached a maximum after 18-h incubation with hGH. Stimulation of DNA synthesis was elicited by hGH in a dose-dependent manner between 0.45 and 45 pmol/l. The activity of the 20 K hGH variant in stimulating DNA synthesis was approx 30% of that of hGH. In contrast, S1-hGH, which lacks a sequence of ten amino acids (140–149) of hGH, showed a 3.2-fold greater activity than hGH. F1 (aminoterminal sequence 1–134 of hGH) was only 0.06% as active as hGH, and the activity of F2 (C-terminal 42 amino acid residue of hGH) was less than 0.01%. Both fragment 1–15 and 32–46 were without effect. The relative potencies of these hGH derivatives in stimulating DNA synthesis were similar to their relative abilities to inhibit [125I]hGH binding to lactogenic receptors on Nb2 cell. Nb2 cells provide a suitable model to study the relationship between receptor binding and the biochemical events induced by lactogens.