ABSTRACT
A synthetic peptide corresponding to the first 34 amino acids of the parathyroid hormone-related protein (PTH-rP) produced by a human tumor associated with hypercalcemia was examined for skeletal and renal effects on calcium metabolism in vivo and in vitro. These effects were compared with those of human parathyroid hormone (1-34), hPTH (1-34). Equal doses of PTH-rP(1-34) and hPTH(1-34) produced equivalent stimulation of adenylate cyclase in vitro in bone cells and kidney cells and tubules. Subcutaneous injection of PTH-rP(1-34) in mice caused a significant dose-related increase in blood ionized calcium similar to that seen with hPTH(1-34) at equivalent doses. Repeated injections of equal doses of both peptides caused sustained hypercalcemia which was significantly greater in PTH-rP(1-34)-treated mice, although each induced comparable increases in histomorphometric indices of osteoclastic bone resorption. PTH-rP(1-34) and hPTH(1-34) also caused similar increases in bone resorption when incubated with fetal rat long bones in organ culture. Infusion of either peptide into thyroparathyroidectomized rats suppressed urinary calcium excretion and increased urinary excretion of cyclic AMP. PTH-rP appears to have similar effects to those of PTH on the skeleton, the kidney, and overall calcium homeostasis.
Subject(s)
Bone Resorption , Calcium/physiology , Kidney Tubules/metabolism , Neoplasm Proteins/pharmacology , Parathyroid Hormone/pharmacology , Peptide Fragments/pharmacology , Adenylyl Cyclases/metabolism , Animals , Calcium/metabolism , Cell Line , Humans , Hypercalcemia/metabolism , Hypercalcemia/pathology , Kidney Tubules/enzymology , Kidney Tubules/pathology , Male , Mice , Neoplasm Proteins/administration & dosage , Parathyroid Hormone/administration & dosage , Parathyroid Hormone-Related Protein , Peptide Fragments/administration & dosage , Rats , TeriparatideABSTRACT
Type II pseudohypoaldosteronism is an uncommonly reported disorder. The authors recently evaluated a patient who in many respects appeared to have this syndrome. He had hyperkalemia, a normal glomerular filtration rate, "normal" serum and urinary aldosterone levels, and low plasma renin activity. In addition, he had a hyperchloremic metabolic acidosis and hypertension. Fractional excretion of potassium was reduced in response to sodium chloride loading. However, renal potassium excretion in response to administration of sodium sulfate was normal. Thiazide diuretic restored the serum potassium, the low bicarbonate, and blood pressure to normal. He developed marked natriuresis and kaliuresis in response to high-dose exogenous mineralocorticoid. The magnitude of the kaliuretic response achieved to exogenous mineralocorticoid has been reported only once previously.