H. Studer and Medizinische Klinik
H. Studer and F. Wyss
H. W. Iff, H. Studer and F. Wyss
A rebound of 131I-uptake by the thyroid gland after a thyrostatic treatment may be taken as evidence of an unimpaired pituitary TSH-secretion.
The iodide uptake in vivo and the iodide accumulation in vitro were studied in rat thyroids following a short-term treatment of the animals with carbimazole. The experiments served as models for the clinical method of assaying the pituitary TSH-reserve.
The total iodide uptake reaches a peak 36 hours after the end of a carbimazole treatment and returns to normal after 96 hours. The rebound of the iodide accumulation has a similar time course. Extending the carbimazole treatment from 6 to 12 days leads to a definite increase in the peak iodide accumulation while the peak of the total iodide uptake was not significantly increased. The duration of the rebound-phase is not changed by prolonged carbimazole treatment.
R. Rohner, H. Studer and M. P. König
H. Kohler, H. Studer, H. Gerber and C. von Grünigen
The hormone content of in vitro iodinated thyroglobulin is a constant fraction of the iodine content of the protein under most, but not all, experimental conditions. In contrast, in vivo iodinated human thyroglobulin may contain as little as 10% or as much as 50% of its total iodine in the T4 molecules. Surprisingly, in some poorly iodinated thyroglobulins up to 30% of the iodine may be found in T4. The mechanism of the apparent dissociation between iodination and coupling efficiency (i.e. percentage of total iodine present as iodothyronines) may be dilution of pre-existing high iodinated thyroglobulin stores by non-iodinated prethyroglobulin. This hypothesis was tested by feeding rats PTU and KClO4 for 9 days and injecting T4 during the last 2 days. Thyroglobulin iodination dropped from 0.9 to 0.13% but the coupling efficiency remained unchanged at 25.7 and 23.9%.
The exchange of highly iodinated thyroglobulin molecules for non-iodinated ones is one of the two in vivo mechanisms suggested so far which can lead to an apparent dissociation of thyroglobulin iodination and couling efficiency.
A. Radvila, R. Roost, H. Bürgi, H. Kohler and H. Studer
Lithium and excess iodide inhibit the release of thyroid hormone from preformed stores. We thus tested the hypothesis that this was due to an inhibition of thyroglobulin breakdown. Rats were pre-treated with propylthiouracil (PTU) for 3 weeks in order to deplete their thyroids of thyroglobulin. While the PTU was continued, lithium chloride (0.25 mEq./100 g weight) or potassium iodide (3 mg per rat) were injected every 12 h for 3 days. Thereafter the thyroglobulin content in thyroid gland homogenates was measured. PTU pre-treatment lowered the thyroglobulin content from 4.21 to 0.22 mg/100 mg gland. Lithium caused a marked re-accumulation of thyroglobulin to 0.60 mg/100 mg within 3 days. While iodide alone had only a borderline effect, it markedly potentiated the action of lithium and a combination of the two drugs increased the thyroglobulin content to 1.04 mg/100 mg.
Thyroxine was injected into similarly pre-treated animals to suppress secretion of thyrotrophic hormone. This markedly inhibited the proteolysis of thyroglobulin and 1.3 mg/100 mg gland accumulated after 3 days. Excess iodide, given in addition to thyroxine, decreased the amount of thyroglobulin accumulated to 0.75 mg/100 mg gland. To study whether this could be explained by an inhibitory action of iodide on thyroglobulin biosynthesis, thyroid glands from animals treated with excess iodide were incubated in vitro in the presence of 0.2 mm iodide for 3 h. Iodide decreased the incorporation of radioactive leucine into total thyroidal protein and into thyroglobulin by 25 and 35 % respectively. Iodide did not inhibit protein synthesis in the kidney, liver or muscle tissue. Thus, large doses of iodide selectively inhibit thyroglobulin biosynthesis.