TY - JOUR
T1 - Animal model of primary hyperparathyroidism
AU - Jaeger, P.
AU - Jones, W.
AU - Kashgarian, M.
AU - Baron, R.
AU - Clemens, T. L.
AU - Segre, G. V.
AU - Hayslett, J. P.
PY - 1987
Y1 - 1987
N2 - An experimental model of hyperparathyroidism was developed in the rat to simulate primary hyperparathyroidism in humans. In this model thyroparathyroidectomized (TPTX) or parathyroidectomized (PTX) animals were infused for 6 days with an amount of bovine synthetic parathyroid hormone (PTH)-(1-34) fragment to restore plasma calcium levels to normal (0.7 U·h-1) or with PTH at twofold (1.4 U·h-1) or threefold (2.1 U·h-1) this basal level. Animals infused with 2.1 U·h-1 of bovine PTH-(1-34) exhibited hypercalcemia, hypophosphatemia, a reduction in theoretical renal threshold for phosphate and an increase in 1,25-dihydroxyvitamin D plasma levels that were approximately threefold the control value. In addition, these animals demonstrated nephrocalcinosis and changes of bone histology that were typical of the findings in patients with primary hyperparathyroidism. In contrast, in animals infused at 1.4 U·h-1, plasma calcium, phosphate, and theoretical renal threshold for phosphate remained within normal limits, but plasma 1,25-dihydroxyvitamin D was increased above control, suggesting that increased activity of 1α-hydroxylase may be the most sensitive index of increased PTH levels. This animal model permits sustained elevation of PTH plasma levels at basal or pathologically elevated levels and should provide an effective means by which to evaluate the consequences of chronic hyperparathyroidism on epithelial function, bone, and other organ systems.
AB - An experimental model of hyperparathyroidism was developed in the rat to simulate primary hyperparathyroidism in humans. In this model thyroparathyroidectomized (TPTX) or parathyroidectomized (PTX) animals were infused for 6 days with an amount of bovine synthetic parathyroid hormone (PTH)-(1-34) fragment to restore plasma calcium levels to normal (0.7 U·h-1) or with PTH at twofold (1.4 U·h-1) or threefold (2.1 U·h-1) this basal level. Animals infused with 2.1 U·h-1 of bovine PTH-(1-34) exhibited hypercalcemia, hypophosphatemia, a reduction in theoretical renal threshold for phosphate and an increase in 1,25-dihydroxyvitamin D plasma levels that were approximately threefold the control value. In addition, these animals demonstrated nephrocalcinosis and changes of bone histology that were typical of the findings in patients with primary hyperparathyroidism. In contrast, in animals infused at 1.4 U·h-1, plasma calcium, phosphate, and theoretical renal threshold for phosphate remained within normal limits, but plasma 1,25-dihydroxyvitamin D was increased above control, suggesting that increased activity of 1α-hydroxylase may be the most sensitive index of increased PTH levels. This animal model permits sustained elevation of PTH plasma levels at basal or pathologically elevated levels and should provide an effective means by which to evaluate the consequences of chronic hyperparathyroidism on epithelial function, bone, and other organ systems.
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U2 - 10.1152/ajpendo.1987.252.6.e790
DO - 10.1152/ajpendo.1987.252.6.e790
M3 - Article
C2 - 3591940
AN - SCOPUS:0023235139
SN - 0193-1849
VL - 252
SP - E790-E798
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 6 (15/6)
ER -