Hidemasa Uchimura

Increased Levels of Serum Angiotensin-Converting Enzyme Activity in Hyperthyroidism

Serum angiotensin-converting enzyme activity was significantly elevated in 21 patients with hyperthyroidism (65 +/- 18 U/mL) as compared with levels in healthy control subjects (30 +/- 9 U/mL). In eight patients treated with thionamide drugs, the enzyme activities decreased to a normal range as thyroid hormone concentrations returned to euthyroid levels. When two patients became hyperthyroid due to an insufficient maintenance dose of antithyroid drugs, the increase in the serum thyroid hormone concentration was followed by the re-elevation of serum angiotensin-converting enzyme levels with a time lag of about 2 weeks. Levels of this enzyme are increased reflecting the elevated serum thyroid hormone levels in hyperthyroidism. The hyperthyroid state should be considered when serum angiotensin-converting enzyme levels are high.

Accumulation of intermediate density lipoprotein in the plasma of cholesterol-fed hypothyroid rats

Abstract The present study aimed to characterize the high cholesterol diet-induced hyperlipoproteinemia developed in thyroidectomized hypothyroid rats, in such animals the activities of hepatic triglyceride lipase having been shown to be decreased. Feeding a diet containing 1% cholesterol to normal control rats resulted in hypercholesterolemia characterized by increases of VLDL, IDL and LDL. The feeding of cholesterol to hypothyroid rats produced a marked accentuation of hypercholesterolemia characterized by a large increase in IDL with a lesser increase in LDL. The IDL contained an increased amount of apo E. The VLDL of cholesterol-fed hypothyroid rats contained β-VLDL. These findings indicate a marked accumulation of remnant lipoproteins in the plasma of cholesterol-fed hypothyroid rats. Putting this and our previous findings together, we suggest that such an accumulation may be caused by impaired removal by the liver of remnant lipoproteins due to the decreased activities of hepatic triglyceride lipase.

Characterization of Receptors for Insulin-Like Growth Factors in Human Brain

The structural properties of receptors for insulin-like growth factors (IGFs) in human brain were studied. Brain membranes were incubated with 125I-IGF-I or II, cross-linked with disuccinimidyl suberate and subjected to electrophoresis under reducing conditions and autoradiography. Two proteins with apparent molecular weights of 120 and 220 kD were specifically labeled. The labeled proteins were immunoprecipitated with monoclonal antibody to type IIGF receptors, indicating that they represent alpha-subunit and its dimer of type IIGF receptor. The size of brain alpha-subunit was smaller than placental alpha-subunit (130 kD). Treatment with N-glycosidase F reduced the brain alpha-subunit from 120 to 95 kD and the placental alpha-subunit from 130 to 105 kD. Neuraminidase decreased the placental alpha-subunit from 130 to 125 kD, but it had no effect on the mobility of the brain alpha-subunit. Solubilized IGF-I receptors from placenta were retained by wheat germ agglutinin and concanavalin A columns, and eluted with the specific sugars. In contrast, solubilized IGF-I receptors from brain did not bind to these columns. These results indicate that human brains have only type IIGF receptors and that the molecular size of the alpha-subunit in brain receptors is smaller than in placental receptors. The size discrepancy may result from the differences in both protein and carbohydrate moieties.

Comparison of the Ability of Thyroxine and Triiodothyronine to Suppress TRH-Induced TSH Secretion by Perifused Rat Anterior Pituitary Fragments

Adenohypophyseal fragments from 8 rats were perifused in small 0.2-ml chambers with medium alone or with medium containing 0.2 or 2 micrograms/dl T3 or 20 micrograms/dl T4. The TSH secretion in response to 1-min perifusion with 3 X 10(-8) M TRH was measured before and at 20- to 40-min intervals after beginning T4 or T3 perifusions. A similar temporal course of inhibition of TRH-induced TSH secretion was produced by both iodothyronines, suggesting but not proving that T4 may inhibit the TSH secretion by a direct effect not dependent on its prior intra- or extrapituitary conversion to T3.

Thyroid hormone secretion is more sensitive than thyroid cyclic AMP accumulation to stimulation with LATS in mice in vitro and in vivo

The effects of LATS-immunoglobulin G (IgG) on thyroid hormone secretion and on thyroid cAMP concentrations were investigated in mice and compared to those of TSH. In the in vitro experiments, thyroid lobes were incubated in Krebs-Ringer bicarbonate buffer with LATS-IgG or TSH for 3 h or 2 h and T3 concentrations in buffer and thyroid cAMP were measured by RIA. T3 in the buffer was increased with 1.5 mg/ml of LATS-IgG (A) or 2.5 mg/ml of LATS-IgG (B) (1000%/5 mg or 400%/5 mg in the McKenzie bioassay, respectively), whereas thyroid cAMP was elevated only after incubation with two to four times higher doses of LATS-IgG (A) or LATS-IgG (B). 0.03 mU/ml of TSH increased T3 concentrations, while a two fold higher dose of TSH was required to increase thyroid cAMP. I n the in vivo study, 5 mg of LATS-IgG (A) injected intravenously increased serum T4 concentrations but not thyroid cAMP. 2 mU of TSH increased serum T4, while 10 mU was needed to elevate thyroid cAMP. These results indicate that: i) thyroid hormone secretion is more sensitive than increases of thyroid cAMP to stimulation with LATS, which is similar to stimulation with TSH and that: ii) thyroid hormone secretion rather than increases of thyroid cAMP should be employed to detect serum thyroid stimulating activities when mouse thyroids are used.

Chronic Effect of TSH on Human Thyroid Tissue in Organ Culture

Abstract The chronic effect of TSH on thyroidal cAMP concentrations and release of thyroid hormones was investigated using human thyroid tissue in organ culture. Normal human thyroid slices were placed in HAMs F-10 synthetic culture medium in Falcon organ tissue culture dishes, and incubated at 37° in a humidified atmosphere of 5% CO2 in air. Medium was changed everyday and daily T3 or T4 release was determined using concentration of T3 or T4 in the medium. After incubation, slices were transferred to the medium containing 10 mM theophylline and incubated without TSH for an additional 30 min to determine thyroidal cAMP concentrations. Thyroidal cAMP concentrations in slices incubated with 10 mU/ml of TSH increased significantly at 2, 6, and 24 hr and even on the 6th day of incubation. Daily T3 release was significantly increased above control from the 3rd day and daily T4 release from the 4th day to the 11th day of incubation with 10 mU/ml of TSH. Histologically, almost all follicles were structurally maintained even on the 11th day of incubation. These results suggest that both thyroidal cAMP concentrations and release of thyroid hormones are stimulated chronically by TSH. This organ culture system is useful for investigating chronic effects of various materials on human thyroid tissue.

Changes in Thyrotropin Binding Inhibiting Immunoglobulins (TBII) in sera of patients with Graves’ disease at the time of relapse or exacerbation

Thyrotropin Binding Inhibiting Immunoglobulins (TBII) were measured in sera of 240 patients with Graves’ disease who were followed 0–25 yr as a cross-sectioned study (21 untreated, 189 under therapy and 30 T3-suppressible and drug-discontinued patients) by using solubilized porcine thyroid TSH receptor. Assays were performed by using 50 μl of serum. All untreated 21 patients showed positive TBII. Frequency of positive patients decreased yearly with treatment although 36% of patients remained positive after 6 yr of therapy. After that time TBII were positive in 61 % of follow-up patients and in 16 positive patients who have been treated for more than 10 yr, drug therapy could not be stopped because of recurrence. TBII were positive in 6 of 30 T3-suppressible patients. As a longitudinal study changes in TBII were studied in 10 patients at the time of relapse or exacerbation. TBII increased in parallel with increases in thyroid hormone concentrations in 3 of 10 patients. Six of the others showed earlier or later TBII increases than those in thyroid hormones. One patient did not show any change in TBII, albeit thyroid hormone concentrations were found to be increased. Our observations suggest that abnormal IgGs detected as TBII in sera of patients with Graves’ disease by the present method do not explain the occurrence of hyperthyroidism.