Hatakeyama Yuriko, Mizunashi Kazutoshi, Furukawa Yohtaro, Yabuki Shigemitsu, Sato Yumi, Igarashi Teruo
Division of Laboratory Medicine, Tohoku University School of Medicine, Aoba-ku, Sendai 980-8574, Japan.
J Clin Endocrinol Metab. 2003 May;88(5):2250-5. doi: 10.1210/jc.2002-021610.
PTH (7-84) has antagonistic effects on the calcemic and phosphaturic actions of PTH (1-84) whole molecule (bioPTH). Human plasma contains bioPTH and PTH (7-84)-like fragments. Using bioPTH-specific and nonspecific assays, we found that the patients with pseudohypoparathyroidism (PHP) type I with PTH-resistant hypocalcemia and hyperphosphatemia had the increased plasma levels of bioPTH and PTH (7-84)-like fragments than normal subjects (26.8 +/- 13.2 vs. 2.37 +/- 0.75 pmol/liter, P < 0.01 and 16.2 +/- 8.8 vs. 0.82 +/- 0.47 pmol/liter, P < 0.01, respectively). Calcitriol treatment increased phosphaturic response to PTH (1-34) (P < 0.05), and there was a negative correlation between phosphaturic response and the PTH levels (P < 0.05). These results suggested that the increased bioPTH and PTH (7-84)-like fragment levels may be related to the impaired phosphaturic response to PTH (1-34) in PHP type I. We also examined bioPTH-calcium dynamics in PHP type Ib patients and found that set-point calcium was 0.928 +/- 0.045 mmol/liter and the baseline to maximal ratio of bioPTH was 0.96 +/- 0.04. Calcitriol treatment increased set-point calcium to 1.129 +/- 0.028 mmol/liter (P < 0.01) and suppressed baseline to maximal ratio of bioPTH to 0.35 +/- 0.21 (P < 0.01). These bio-PTH calcium dynamics studies revealed the maximally stimulated baseline PTH secretion in PHP type Ib and demonstrated the effects of calcitriol on PTH-calcium curve shift and the degree of relative stimulation of baseline secretion.
甲状旁腺激素（7 - 84）对甲状旁腺激素（1 - 84）全分子（生物活性甲状旁腺激素）的血钙调节和促尿磷排泄作用具有拮抗作用。人血浆中含有生物活性甲状旁腺激素和甲状旁腺激素（7 - 84）样片段。通过生物活性甲状旁腺激素特异性和非特异性检测，我们发现，患有甲状旁腺功能减退症（PHP）I型且伴有甲状旁腺激素抵抗性低钙血症和高磷血症的患者，其血浆中生物活性甲状旁腺激素和甲状旁腺激素（7 - 84）样片段的水平高于正常受试者（分别为26.8±13.2与2.37±0.75 pmol/升，P<0.01；以及16.2±8.8与0.82±0.47 pmol/升，P<0.01）。骨化三醇治疗增加了对甲状旁腺激素（1 - 34）的尿磷排泄反应（P<0.05），并且尿磷排泄反应与甲状旁腺激素水平之间存在负相关（P<0.05）。这些结果表明，生物活性甲状旁腺激素和甲状旁腺激素（7 - 84）样片段水平的升高可能与PHP I型中对甲状旁腺激素（1 - 34）的尿磷排泄反应受损有关。我们还研究了PHP Ib型患者的生物活性甲状旁腺激素 - 钙动力学，发现设定点钙为0.928±0.045 mmol/升，生物活性甲状旁腺激素的基线与最大值之比为0.96±0.04。骨化三醇治疗使设定点钙增加至1.129±0.028 mmol/升（P<0.01），并将生物活性甲状旁腺激素的基线与最大值之比抑制至0.35±0.21（P<0.01）。这些生物活性甲状旁腺激素 - 钙动力学研究揭示了PHP Ib型中最大刺激下的基线甲状旁腺激素分泌情况，并证明了骨化三醇对甲状旁腺激素 - 钙曲线移位以及基线分泌相对刺激程度的影响。
