Radioisotopes have been widely used in both in vitro and in vivo studies of endocrine organs. In this lecture, results of our recent in vitro studies on calcium regulating hormones, thyroid-stimulating hormone, and gastro-intestinal hormones are reviewed.
1) Clinical evaluation of measurement of calcium regulating hormones such as PTH, calcitonin and vitamin D metabolites was demonstrated. Furthermore, problems of those assays were also discussed. Especially, simpler methods which measure intact PTH or vitamin D metabolites are to be developed. PTH-like factor, which should play the major role in hypercalcemia of malignancy, was assayed biologically. After determination of amino-acid sequence of this protein, clinical measurement should reveal mechanism of hypercalcemia of malignancy.
2) Studies on TSH-receptor antibodies by using radioreceptor assay. TSH-binding inhibitor immunoglobulins (TBII) were detected not only in 93% of untreated patients with Graves' disease, but also in 21% of patients with primary myxedema. In contrast to the thyroid-stimulating nature of TBII in Graves' patients, TBII in hypothyroid patients were disclosed to be blocking in their nature. Clinical and laboratory findings supported pathogenetic role of the blocking antibodies in the latter condition.
3) Mutual regulation between CCK and muscarinic receptors on dispersed pancreatic acini. CCK and carbachol in their higher concentrations regulated muscarinic receptor and CCK receptor, respectively. The mode of regulation of both receptors was disappearance of their high affinity binding site. TPA, an activator of protein kinase C, modulated both receptors in the same manner as CCK or carbachol. These effects of CCK and carbachol on receptors were well compatible to the restriction of carbachol or CCK induced amylase secretion by CCK or carbachol.
These in vitro studies, in association with the results of in vivo studies, contribute to the developments of nuclear endocrinology.
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