Actions of parathyroid hormone and parathyroid hormone-related protein.

Published on Jan 1, 1992in Journal of Endocrinological Investigation4.256
René Rizzoli116
Estimated H-index: 116
,
S. Ferrari19
Estimated H-index: 19
+ 2 AuthorsJ. P. Bonjour2
Estimated H-index: 2
Source
Abstract
: By interacting with a structurally identical receptor, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) display a common spectrum of action on the transport of mineral elements in bone and kidney. In vivo, PTH/PTHrP similarly reduce the renal tubular reabsorption of inorganic phosphate (Pi) and increase that of calcium. The hypercalcemic effect of PTHrP is due to an increase in both bone resorption and renal calcium reabsorption, the latter through a sodium-independent mechanism. The PTHrP-stimulated bone resorption can be totally inhibited by bisphosphonate therapy. Despite that, the fall in calcemia is moderate, indicating that the PTHrP main hypercalcemic action is due to the stimulation of the renal transport of calcium. For identical effects on renal ionic transports, PTHrP appears to less stimulate bone formation than PTH. These experimental findings are similar to clinical observations in patients with primary hyperparathyroidism or with solid malignant tumors. In vitro, the effects of PTH(1-34), PTHrP(1-34) and PTHrP(1-141) on cAMP production and sodium-dependent phosphate transport (NaPiT) are similar in kidney cells, where NaPiT is specifically inhibited by either peptide. This effect is attenuated by the competitive inhibitor [D-Trp12,Tyr34]bPTH(7-34)amide. Transforming growth factor-alpha similarly modulates the cAMP and NaPiT responses to PTH/PTHrP. In cultured mammary cells isolated from lactating rats, PTHrP elicits a 2-fold increase of cAMP production. Various products of bone and stromal cells, and of leukocytes, such as Interleukin-6 or Tumor necrosis factor-alpha, as well as high extracellular calcium concentration enhance PTHrP production by cultured lung squamous cell carcinoma and Leydig tumor cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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Parathyroid hormone-related protein (PTHrP) can simulate most of the actions of parathyroid hormone (PTH) including increases in bone resorption and distal tubular calcium reabsorption and inhibition of proximal tubular phosphate transport.1 The low serum phosphate in parallel with low circulating PTH is consistent with PTHrP involvement in this case. Whether it can be causative for a serum calcium of 6.24 mmol/L however is a moot point. While the mechanism underlying the patient’s severe hyperc...
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