Kifor O, Moore F D, Wang P, Goldstein M, Vassilev P, Kifor I, Hebert S C, Brown E M
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
J Clin Endocrinol Metab. 1996 Apr;81(4):1598-606. doi: 10.1210/jcem.81.4.8636374.
Most parathyroid adenomas and some pathological parathyroid glands from patients with primary parathyroid hyperplasia or severe uremic secondary/tertiary hyperparathyroidism show an elevated set-point [the extracellular Ca2+ concentration (Ca2+o) half-maximally inhibiting PTH secretion]. In the present study, we investigated whether expression of the Ca2+o-sensing receptor protein recently cloned from bovine parathyroid, a key component in Ca2+o-regulated PTH release, is altered in primary and uremic hyperparathyroidism. Using immunohistochemistry 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 glands from 2 individuals with uremic hyperparathyroidism. The results show a substantial reduction in the intensity of immunostaining for the receptor protein that averaged nearly 60% for both adenomas and hyperplastic glands, as quantitated by image analysis. Although normal glands from normocalcemic controls were not available, the intensity of receptor staining in normal glands from patients with adenomas was comparable to that in normal bovine, rat, and mouse parathyroid glands. There was considerable variation in staining intensity among different pathological parathyroid glands, even in those from the same patient with secondary hyperparathyroidism. In addition, both adenomas and hyperplastic glands had, in some cases, isolated chief cells and groups of cells, sometimes around the periphery of an abnormal gland, with receptor staining equivalent to that of normal parathyroid cells, whereas the bulk of the cells in the same gland showed a marked decrease in staining. Thus, there is a variable, but substantial, reduction in the immunoreactivity of the Ca2+o-sensing receptor protein in both parathyroid adenomas and uremic hyperparathyroidism, as assessed by immunohistochemistry, that probably results from reduced expression of the receptor protein and may contribute to the increase in the set-point often observed in these patients.
大多数甲状旁腺腺瘤以及一些来自原发性甲状旁腺功能亢进或严重尿毒症继发性/三发性甲状旁腺功能亢进患者的病理性甲状旁腺显示设定点升高[细胞外Ca2+浓度（Ca2+o）对甲状旁腺激素（PTH）分泌产生半数最大抑制作用时的浓度]。在本研究中，我们调查了最近从牛甲状旁腺克隆出的Ca2+o-感受受体蛋白（Ca2+o调节PTH释放的关键成分）的表达在原发性和尿毒症性甲状旁腺功能亢进中是否发生改变。我们使用特异性抗受体抗体进行免疫组织化学，比较了14个腺瘤、同一组患者的24个正常腺体活检组织以及2例尿毒症性甲状旁腺功能亢进患者的8个增生性甲状旁腺中受体蛋白的免疫反应性。结果显示，通过图像分析定量，腺瘤和增生性腺体中受体蛋白的免疫染色强度大幅降低，平均降低近60%。虽然无法获取血钙正常对照者的正常腺体，但腺瘤患者的正常腺体中受体染色强度与正常牛、大鼠和小鼠甲状旁腺中的相当。不同病理性甲状旁腺之间的染色强度存在相当大的差异，即使是来自同一继发性甲状旁腺功能亢进患者的腺体也是如此。此外，在某些情况下，腺瘤和增生性腺体中都有孤立的主细胞和成组细胞，有时在异常腺体的周边，其受体染色与正常甲状旁腺细胞相当，而同一腺体中的大部分细胞染色明显减少。因此，通过免疫组织化学评估，甲状旁腺腺瘤和尿毒症性甲状旁腺功能亢进中Ca2+o-感受受体蛋白的免疫反应性均有可变但显著的降低，这可能是由于受体蛋白表达减少所致，并且可能导致这些患者中经常观察到的设定点升高。
