Employing a cytochemical bioassay, we compared parathyroid function in normal and X-linked hypophosphatemic (Hyp) mice. Under basal conditions Hyp mice manifested
hypocalcemia and, in accord, had a plasma bioactive
parathyroid hormone concentration (3.04 +/- 0.14 pg/ml) significantly greater than that of normals (2.16 +/- 0.14 pg/ml). We confirmed the validity of the bioassay by demonstrating that the plasma collected from both mouse models diluted parallel to the assay standard curve. Moreover, after
parathyroidectomy, normal and Hyp mice had plasma bioactive
parathyroid hormone levels approximately 90% less than those obtained under basal conditions and indistinguishable from one another. In further studies we observed that
dietary calcium and/or
vitamin D deprivation in both animal models resulted in a comparable decline of the plasma
calcium concentration. However, the concordant increase of the circulating bioactive
parathyroid hormone level was greater in the normal mice. Thus, the bioactive
parathyroid hormone concentration obtained in response to a low
calcium challenge in normals was significantly greater than that in Hyp mice. In contrast, in response to
dietary calcium loading, the plasma bioactive
parathyroid hormone levels did not decrease significantly from basal values in either animal model. These data illustrate that the bioactive
parathyroid hormone concentration in both normal and Hyp mice is inversely correlated with the plasma
calcium. However, while the Hyp mice maintain an elevated plasma
parathyroid hormone concentration under basal conditions (in response to a decreased plasma
calcium), the parathyroid activity of the mutants after a more severe hypocalcemic challenge is attenuated, resulting in a significantly different model of linear correlation. Thus, these data indicate that Hyp mice manifested abnormal regulation of parathyroid function.