Polypeptide Hormones and Calcium Metabolism

SUMMARY

Recent studies have expanded remarkably our understanding of the chemistry, physiology, mechanism of action, and clinical importance of the polypeptides—parathyroid hormone and thyrocalcitonin (calcitonin)—the principal hormones regulating calcium metabolism. Thyrocalcitonin, a hormone inducing hypocalcemia and hypophosphatemia, has been isolated, analyzed for amino acid sequence, and synthesized chemically. It is secreted from the parafollicular cells found in mammalian thyroid but related embryologically to the ultimobranchial body of lower vertebrate species. Sensitive radioimmunoassays for thyrocalcitonin and parathyroid hormone have shown that secretion of each is controlled by calcium.

Current findings show that the major physiological actions of parathyroid hormone are mediated by adenosine 3′,5′-monophosphate (cyclic AMP) produced as a consequence of direct, specific hormonal stimulation of the enzyme adenyl cyclase in bone and kidney. Thyrocalcitonin acts through another mechanism to inhibit bone resorption. In normal subjects, but not in pseudohypoparathyroidism, parathyroid hormone causes a marked increase in urinary excretion of cyclic AMP. This observation forms the basis for a useful diagnostic test and suggests that the metabolic abnormality of pseudohypoparathyroidism may be attributable to a genetic lack or defect of a specific adenyl cyclase in renal and skeletal tissue.