Kawata Takehisa, Imanishi Yasuo, Kobayashi Keisuke, Onoda Naoyoshi, Takemoto Yoshiaki, Tahara Hideki, Okuno Senji, Ishimura Eiji, Miki Takami, Ishikawa Tetsuro, Inaba Masaaki, Nishizawa Yoshiki
Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
J Clin Endocrinol Metab. 2005 Oct;90(10):5774-8. doi: 10.1210/jc.2005-0243. Epub 2005 Jul 26.
Although serum calcium (Ca2+) concentration regulates the generation of amino-terminally (N-terminally) truncated forms of human PTH (hPTH) degraded from (1-84)hPTH, no studies have yet reported whether the parathyroid gland itself is responsible for this process.
Our objective was to determine the site of N-terminal truncation and its roles in PTH metabolism in parathyroid cells in vitro.
The effect of extracellular Ca2+ concentration was examined on N-terminal truncation in primary cultured parathyroid cells. The parathyroid glands were obtained from the patients with primary and uremia-associated secondary hyperparathyroidisms who underwent therapeutic parathyroidectomies.
The N-terminally truncated fragments were detectable with commercially available intact PTH (I-PTH) assays, but not with the bio-intact PTH (Bio-PTH) assay, which detected only the (1-84)hPTH. HPLC revealed that generation of N-terminally truncated fragments detectable by I-PTH increased with extracellular Ca2+ concentration. Suppression of PTH secretion by increasing the extracellular Ca2+ concentration was more evident with the Bio-PTH assay than with the I-PTH assay for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism. The Bio-PTH/I-PTH ratio, which is the ratio of (1-84)hPTH to the sum of (1-84)hPTH and N-terminally truncated fragments, decreased in response to increases in extracellular Ca2+.
These findings suggest that the N-terminal truncation is regulated by extracellular Ca2+ concentration and works to suppress the generation of (1-84)hPTH in parathyroid cells.
尽管血清钙（Ca2+）浓度调节从人甲状旁腺激素（hPTH）（1-84）降解产生的氨基末端（N末端）截短形式的生成，但尚无研究报道甲状旁腺本身是否负责这一过程。
我们的目的是确定体外甲状旁腺细胞中N末端截短的位点及其在甲状旁腺激素代谢中的作用。
检测细胞外Ca2+浓度对原代培养甲状旁腺细胞N末端截短的影响。甲状旁腺取自接受治疗性甲状旁腺切除术的原发性和尿毒症相关性继发性甲状旁腺功能亢进患者。
用市售的完整甲状旁腺激素（I-PTH）检测法可检测到N末端截短片段，但用生物完整甲状旁腺激素（Bio-PTH）检测法检测不到，后者仅检测（1-84）hPTH。高效液相色谱法显示，I-PTH可检测到的N末端截短片段的生成随细胞外Ca2+浓度增加而增加。对于由甲状旁腺腺瘤和尿毒症相关性继发性甲状旁腺功能亢进制备的培养甲状旁腺细胞，通过增加细胞外Ca2+浓度抑制甲状旁腺激素分泌在Bio-PTH检测法中比在I-PTH检测法中更明显。Bio-PTH/I-PTH比值，即（1-84）hPTH与（1-84）hPTH和N末端截短片段总和的比值，随细胞外Ca2+增加而降低。
这些发现表明，N末端截短受细胞外Ca2+浓度调节，并在甲状旁腺细胞中抑制（1-84）hPTH的生成。
