Role Of Calcitonin Research Articles

Renal tubular transport of calcium and phosphate in snakes: Role of calcitonin

The effect of acute doses of salmon or porcine calcitonin upon serum values and renal excretion of calcium and phosphate was studied in sham-operated or parathyroidectomized water snakes of the genus Natrix. In intact animals, calcitonin appeared to have no significant effect upon the serum values or the renal clearance of phosphate. In the parathyroidectomized animals, calcitonin caused a depression of serum phosphate values and a slight increase in relative renal phosphate clearance ( C PO 4 C In ). Calcium values and glomerular filtration rates were not altered in either group. The effect of calcitonin upon phosphate excretion in snakes seems to be of minimal importance compared to that of parathyroid hormone.

Calcium and phosphorus metabolism in chronic uremia.

In chronic uremia, the clinical disorders o calcium and phosphorus metabolism are influenced by the following factors: (1) intestinal absorption of calcium and phosphate, resulting in a negative calcium and phosphate balance at normal dietary intakes; (2) renal handling of calcium and phosphate: the fractional transport of calcium (the isoosmotic reabsorption taking place in the proximal tubule) is not affected by GFR modifications, whereas the Tm-limited reabsorption is severely impaired; the external phosphate balance is kept, even in the presence of a reduced nephron population, by means of a proportional reduction in TmPO4 values; (3) physiochemical state and turnover of body calcium and phosphate: in uremic patients, the distribution spaces, turnover rate of calcium, and accretion rate of bones are increased in comparison with the controls; the calcium infusion test in patients with renal osteomalacia is followed by a regular increase in plasma [PO4], whereas a significant decrease is observed in patients with renal osteitis fibrosa, due to the extreme 'avidity' of bones for calcium phosphate; the role of hyperphosphatemia is critical in keeping the plasma [Ca] lower than the expected values for a given metabolic set; moreover, an increased cell uptake of phosphate could counteract to some extent the reduced renal clearance of phosphate; (4) structural and biochemical modifications of bone tissue: uremic osteodystrophy consists mainly of two components: (a) osteomalacia, with osteoid excess, disappearance of the calcification front, and diffuse pathologic mineralization, and (b) osteitis fibrosa, with severe resorption of normally mineralized bone, slight osteoid excess, and almost normal calcification front; (5) hormonal factors: chronic stimulation of parathyroid glands may result in suppressible or even autonomous hyperparathyroidism. As to vitamin D, it has been suggested that the uremic kidney is not able to synthesize the 1,25-di-OH-cholecalciferol, the active metabolite of vitamin D: this results in an impaired intestinal absorption of calcium. On the contrary, the role of calcitonin in chronic uremia is still uncertain, since low values of plasma [Ca] are usually observed.

Kidney and Calcitonin

Calcitonin, whatever its origin, produces a decrease in the renal tubular reabsorption of sodium, phosphate and calcium in man and in the rat. Renal receptors for calcitonin have been demonstrated in the membranes of rat tubular cells using 125I salmon calcitonin as a tracer. Hormone-receptor interaction initiates the activation of membrane adenyl cyclase. In the rat and in man, the kidney plays a major role in degradation of both human and salmon calcitonin. Plasma levels of immunoreactive calcitonin are high in chronic renal failure. The question of the physiological role of calcitonin on kidney function is still unsettled.

TREATMENT OF PAGET'S DISEASE OF BONE WITH PORCINE CALCITONIN

Three patients with Paget's disease of bone have been treated for periods of 8 to 18 months with daily injections of porcine calcitonin. In all patients there were substantial decreases in the biochemical indices of increased bone turnover. In two of the patients symptomatic relief of bone pain was obtained, and in one patient there was histological evidence of formation of normal bone after 12 months’ treatment. The possible role of calcitonin in treating Paget's disease is discussed.

THE RELATIONSHIP BETWEEN FOOD, GASTRO-INTESTINAL HORMONES AND CALCITONIN SECRETION

SUMMARY The role of calcitonin (CT) in postprandial calcium homeostasis and the possibility of a gastroentero-thyroid C-cell system was studied in young pigs. When pigs were fasted for more than 36 h and then fed, the plasma calcium concentration decreased by 6·1% over a period of 60–120 min after a meal. Since in thyroidectomized pigs the plasma calcium concentration increased by 7·2% when they were fed after a fast of 36 h it is suggested that increased CT secretion assists in the control of postprandial hypercalcaemia. Direct measurement of CT in peripheral plasma supported this suggestion. Because the plasma calcium concentration in an intact pig on a normal feeding regime does not change after a meal, the possibility of the involvement of one or more humoral factors in the stimulation of thyroid C-cells was investigated. Exogenous gastrin and endogenous gastrin stimulated by meat extract were both previously shown by us to increase CT secretion rate. This observation has now been extended to include other stimuli to endogenous gastrin, e.g. glycine and gastric distension. Furthermore, partially purified enteroglucagon increased CT secretion rate from perfused thyroid glands, isolated in situ. Stimulation of endogenous entero-glucagon by the intraduodenal administration of glucose, and probable stimulation of endogenous pancreozymin by intraduodenal fat, were both associated with an increased CT secretion rate from the thyroid gland. These results support the concept of a gastroentero-thyroid C-cell system which serves to stimulate CT secretion and thus to protect the skeleton from excessive bone resorption during periods of dietary sufficiency.

The effect of calcium infusion and calcitonin on plasma phosphate in sham-operated and thyroparathyroidectomized dogs.

The effect of iv calcium infusion (1.6 mg Ca/min as acetate or chloride) on plasma phosphate concentration was studied in dogs. Comparisons were made between sham-operated (TI), thyroparathyroidectomized (TPTX), and TPTX dogs administered calcitonin (50 MRC U × 2) during the calcium infusion. In anesthetized animals infused with calcium, a rise in plasma phosphate values was seen only in TPTX dogs. Subcutaneous calcitonin administration prevented this rise in TPTX dogs. Saline-infused controls, and urinary excretion measurements support the conclusion that the effects observed did not result from the presence or absence of parathyroid hormone. The results of these experiments demonstrate that calcitonin, from either endogenous or exogenous sources, prevents or reduces the rise in plasma phosphate concentration which would otherwise occur following calcium infusion in this species. This study supports the recent finding in rats that an important previously unrecognized role of calcitonin may be to moderate...

MECHANISM OF HYPOCALCÆMIA AFTER THYROIDECTOMY FOR THYROTOXICOSIS

The widely accepted hypothesis that parathyroid damage is sufficient to explain the hypocaicæmia which may follow thyroidectomy for thyrotoxicosis cannot be supported. Postoperative hypocalcæmia is related to the age of the patient, the size of the thyroid remnant, and previous thyroid overactivity. Evidence is presented from patients with known parathyroid damage that the postoperative hypocalcæmia in thyrotoxic patients cannot be explained solely on the basis of surgical interference with the parathyroids. A detailed postoperative balance study in a young thyrotoxic man showed avid calcium retention in the first month after operation. A prospective study of thyrotoxic patients showed evidence of bone disease in the majority. The serum-alkaline-phosphatase may be regarded as an index of thyrotoxic osteodystrophy, and it is suggested that when serum-alkaline-phosphatase levels are raised, calcium supplements might be considered as part of the preoperative preparation of the thyrotoxic patient. No evidence to support the possible role of calcitonin as a factor in producing hypocalcæmia after thyroidectomy for thyrotoxicosis has been found. It is considered that the term " hypoparathyroidism " is misleading when used for hypocalcæmia developing within one or two days of thyroidectomy in thyrotoxic patients.

Effect of calcitonin on serum inorganic sulphate and on the disappearance of injected radioactive sulphate in the rat.

SUMMARY In an investigation of the possible role of calcitonin in the metabolism of glycosaminoglycans it was found that the hormone increased the rate of disappearance from serum of [35S]sulphate injected into rats. No excessive deposition of radioactive sulphate was found in bone, kidney, liver or ventricular myocardium of calcitonin-treated rats. Calcitonin also rapidly lowered serum inorganic sulphate levels. Both effects were prevented by previous nephrectomy, leading to the conclusion that calcitonin acts on the kidney to promote the excretion of inorganic sulphate.