The relationship between the actions of vitamin D, parathyroid hormone and calcitonin.
ABSTRACT The effect of PTH and CT upon hydroxyproline and electrolyte excretion, plasma calcium and phosphate, calcium balance, and the excretion of radiocalcium was examined in vitamin D-deficient thyroparathyroidectomized rats. The results were compared to those obtained in D-fed animals. An increase in urinary hydroxyproline, which persisted for many hours, occurred in D-deficient animals approximately 30 h after thyroparathroidectomy, but was not seen in D-fed animals. It was suppressed by high calcium infusion. Infusion of PTH or CT increased the hydroxyprolinuria even further in D-deficient animls. PTH increased hydroxyprolinuria in D-fed animals, but CT caused a significant decrease. In the D-deficient animals both PTH and CT caused a decrease in urinary calcium excretion, and an increase of the already positive calcium balance. In D-fed animals CT had similar effects, but PTH caused a significant increase in calcium excretion and a negative calcium balance. Young animals injected with45Ca while on a D-deficient diet were studied 3 weeks later at a time when they had developed D-deficiency. When these animals were thyroparathyroidectomized and maintained on a constant glucose and electrolyte perfusion, the excretion of calcium was relatively constant and the specific activity of urnary calcium declined only slightly over a 28 h period. When PTH was given, both total and radioactive calcium excretion diminished initially, leading to a significant decrease in specific activity. The specific activity declined for the first 3 h of hormone infusion, then rose gradually and became greater than normal during the last 4 h of hormone infusion. When CT was given with PTH, total calcium excretion fell and remained below the control rate throughout the experiment. Specific activity rose markedly during the first 2 h, then fell rapidly to values below the control levels for the remainder of the experiment.
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ABSTRACT: This study examined the role of cyclic AMP in the phosphaturic response to parathyroid hormone in vitamin D-deficient rats. Infusion of purified bovine parathyroid hormone (13.3 mug/h) into control, D-fed, or D-deficient, thyroparathyroidectomized rats produced a sixfold increase in renal phosphate and cyclic AMP excretion in D-fed rats, but only a two- to threefold increase in both parameters in D-deficient animals. Intravenous injection of parathyroid hormone over the dosage range from 1-50 mug/kg resulted in a dose-dependent increase in phosphate and cyclic AMP excretion with both D-fed and D-deficient thyroparathyroidectomized rats. However, the D-deficient rats responded to these injections of parathyroid hormone with a two- to threefold increase in both renal phosphate and cyclic AMP excretion at the highest dose of 50 mug/kg, whereas the D-fed animals' response was 35-fold and 11-fold over control excretion levels of phosphate and cyclic AMP, respectively. To directly examine the role of the renal cortical adenylate cyclase system in the blunted phosphaturic and urinary cyclic AMP responses to parathyroid hormone in D-deficient rats, we prepared a plasma membrane fraction enriched in this enzyme activity from the renal cortex of D-fed and D-deficient thyroparathyroidectomized rats. The renal cortical adenylate cyclase of D-deficient rats showed significantly (P less than 0.001) less activation by parathyroid hormone over the hormone concentration range from 0.3 to 7.0 mug/ml than was observed with the enzyme prepared from D-fed animals. Basal adenylate cyclase activity and the fluoride-stimulated enzyme activity were not altered by the state of D-deficiency. These experiments demonstrate that the blunted phosphaturic response to parathyroid hormone observed in D-deficient rats is associated with the reduced responsiveness of the renal cortical adenylate cyclase to the hormone. Moreover, the defect in the renal membrane adenylate cyclase system appears to be localized at the level of PTH binding to membrane receptors or, alternatively, at the level of transmission of the hormone-receptor binding signal to the catalytic moiety of this membrane enzyme.Journal of Clinical Investigation 04/1976; 57(3):559-68. · 12.81 Impact Factor
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ABSTRACT: The presence of hyperparathyroidism in early renal failure was first suggested by the data of Friis, Hahnemann and Weeke  which showed that serum phosphate was lower in patients with small decreases in glomerular filtration rate (GFR) (< 40 ml/min) than in a control group of normals. Also, Popovtzer et al  showed that the urinary calcium excretion was lower than normal in a similar group of patients. This hyperparathyroidism was demonstrated directly by Reiss, Canterbury and Egdahl , who found significantly increased serum immunoreactive parathyroid hormone (iPTH) levels at GFR values as high as 70 to 80 ml/min. Data from my laboratory regarding this point are shown in Fig. 1. But our data differ from those of Reiss, Canterbury and Egdahl  in that significant increases in serum iPTH were first noted at inulin clearance values below 40 ml/min. This difference may be related in some way to the immunoheterogeneity of serum iPTH, which will be discussed later in the section on the radioimmunoassay of PTH. The important points to be derived from these studies, however, are that secondary hyperparathyroidism begins early and that its severity is related, in general, to the degree of renal functional impairment, as originally suggested by Berson and Yalow  who were the first to demonstrate that serum iPTH was increased in renal failure.Kidney International 09/1973; 4(2):89-95. · 8.52 Impact Factor
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ABSTRACT: Five patients who had gross abnormalities of calcium and phosphorus metabolism due to long standing renal failure are described to illustrate the difficulties with the term "tertiary hyperparathyroidism". One patient who had unequivocal biochemical tertiary hyperparathyroidism was found histologically to have nodular hyperplasia of all four glands even though one gland weighed twice as much (12g) as the combined weight of the other three. Another patient was not hypercalcaemic but had all the other features of the condition including rapid onset of osteitis fibrosa, vascular calcification and a probable parathyroid adenoma, with hyperplasia of the three glands. The other three had hypercalcaemia only after a reduction in the plasma inorganic phosphorus due either to renal transplantation or aluminum hydroxide therapy. The bone histology of the five patients varied from severe osteomalacia to severe osteitis fibrosa. A consideration of the factors involved in causing hypercalcaemia in these patients and a review of the literature leads to the conclusion that the term tertiary hyperparathyroidism is often misleading and best avoided.Australian and New Zealand journal of medicine 01/1976; 5(6):551-6.