REDUCED IMMUNOSTAINING FOR THE EXTRACELLULAR CA SENSING RECEPTOR IN PRIMARY AND UREMIC SECONDARY HYPERPARATHYROIDISM

Most parathyroid adenomas and some pathological parathyroid glands fro m patients with primary parathyroid hyperplasia or severe uremic secon dary/tertiary hyperparathyroidism show an elevated set-point [the extr acellular Ca2+ concentration (Ca-0(2+)) half-maximally inhibiting PTH secretion]. In the present study, we investigated whether expression o f the Ca-0(2+)-sensing receptor protein recently cloned from bovine pa rathyroid, a key component in Ca-0(2+)-regulated PTH release, is alter ed in primary and uremic hyperparathyroidism. Using immunohistochemist ry with specific antireceptor antibodies, we compared immunoreactivity of the receptor protein in 14 adenomas, biopsies of 24 normal glands from this same group of patients, and 8 hyperplastic parathyroid gland s from 2 individuals with uremic hyperparathyroidism. The results show a substantial reduction in the intensity of immunostaining for the re ceptor protein that averaged nearly 60% for both adenomas and hyperpla stic glands, as quantitated by image analysis. Although normal glands from normocalcemic controls were not available, the intensity of recep tor staining in normal glands from patients with adenomas was comparab le to that in normal bovine, rat, and mouse parathyroid glands. There was considerable variation in staining intensity among different patho logical parathyroid glands, even in those from the same patient with s econdary hyperparathyroidism. In addition, both adenomas and hyperplas tic glands had, in some cases, isolated chief cells and groups of cell s, sometimes around the periphery of an abnormal gland, with receptor staining equivalent to that of normal parathyroid cells, whereas the b ulk of the cells in the same gland showed a marked decrease in stainin g. Thus, there is a variable, but substantial, reduction in the immuno reactivity of the Ca-0(2+)-sensing receptor protein in both parathyroi d adenomas and uremic hyperparathyroidism, as assessed by immunohistoc hemistry, that probably results from reduced expression of the recepto r protein and may contribute to the increase in the set-point often ob served in these patients.