Abstract:
:One of the hypotheses attempting to explain the etiology of the human disease X-linked hypophosphatemia (XLH) posits renal hypersensitivity to parathyroid hormone (PTH). These studies were designed to test this hypothesis in vivo, using the hemizygous hypophosphatemic (Hyp/Y) mouse as an animal model for XLH. Vehicle or 1.0 U bovine PTH (bPTH)/g BW sc was given to intact normal or Hyp mice. Two hours later a small but significant hypercalcemia was observed in both genotypes. Only normal mice remained hypercalcemic 5 h after injection. Intact normal mice, but not Hyp mice, displayed a significant bPTH-induced hypophosphatemia. Administration of bPTH caused a significant increase in both fractional excretion of phosphate (FE-P) and urinary cAMP (UcAMP) 2 h after injection. However, there was no significant differences in the magnitude of response between genotypes. In a different experiment hPTH dose-response curves (0, 0.04, 0.2, and 1.0 U bPTH/g BW sc) were constructed in normal and Hyp mice 18 h after thyroparathyroidectomy (TPTX). bPTH caused a significant hypercalcemia and hypophosphatemia in TPTX normal mice at all doses 2 h after injection. But only the highest dose of hormone caused a significant hypercalcemia in TPTX Hyp mice, and no dose caused a significant decrease in plasma P. In both genotypes a dose-dependent increase in FE-P and UcAMP was observed 2 h after bPTH administration. As with intact mice, there was no indication of a hypersensitive or exaggerated renal response in TPTX Hyp mice. In summary, results from these in vivo experiments indicate that the kidneys of Hyp mice are not hypersensitive to exogenous bPTH. Furthermore, TPTX Hyp mice appeared to exhibit "skeletal resistance" to exogenous PTH, as do osteomalacic dogs and humans. We conclude that renal hypersensitivity to PTH does not play a role in the etiology of XLH in Hyp mice.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Kiebzak GM,Meyer RA Jrdoi
10.1210/endo-110-3-1030subject
Has Abstractpub_date
1982-03-01 00:00:00pages
1030-6issue
3eissn
0013-7227issn
1945-7170journal_volume
110pub_type
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