Suppression of PTH and decreased action on bone are partially responsible for the low calcemic activity of 22-oxacalcitriol relative to 1,25-(OH)2D3.
Suppression of PTH and decreased action on bone are partially responsible for the low calcemic activity of 22-oxacalcitriol relative to 1,25-(OH)2D3.
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PTH 的抑制和对骨作用的降低是 22-奥沙骨化三醇相对于 1,25-(OH)2D3 的低钙血活性的部分原因。
DOI：
10.1002/jbmr.5650070713
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Slatopolsky,E
中科院分区：
文献类型：
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作者：
Finch,JL;Brown,AJ;Mori,T;Nishii,Y;Slatopolsky,E
我们之前表明，OCT（一种 1,25-(OH)2D3 的类似物，几乎没有钙血活性）可以降低正常大鼠的 PTH mRNA 水平，并抑制培养的牛甲状旁腺细胞中 PTH 的分泌，其效力与 1,25-(OH)2D3 相同，并且在正常钙饮食的正常大鼠中，给予 OCT（500 ng）5 天不会增加血浆 Ca。因此，为了确定 OCT 抑制 PTH 是否导致其缺乏钙血活性，并进一步表征 OCT 对钙代谢的影响，我们在甲状旁腺切除 (PTX) 大鼠中进行了几项研究。 PTX 大鼠维持正常饮食（0.9% Ca），每天注射媒介物、1,25-(OH)2D3（200 ng/天）或 OCT（200 ng/天），持续 6 天。每天测量血浆 Ca。对照组大鼠的血浆 Ca 保持在 6.60 至 7.40 mg/dl 之间，而 1,25-(OH)2D3 治疗的大鼠中 Ca 增加至 12.9 ± 0.42 mg/dl，OCT 治疗的大鼠在 6 天后增加至 9.53 ± 0.35 mg/dl。在缺钙饮食中，对照大鼠将血浆 Ca 维持在 4.25 至 4.60 mg/dl 之间，但使用 1,25-(OH)2D3 时，Ca 增加至 13.7 ± 0.24 mg/dl，使用 OCT 时，Ca 增加至 7.29 ± 0.17 mg/dl。由于两种饮食中 OCT 导致的 Ca 升高相似，因此 OCT 似乎主要作用于骨骼。 PTX 大鼠通过 Alzet 泵输注 PTH（1.84 μg/kg/天）以达到正常血浆 Ca，然后每天用载体或 OCT（200 ng/天）进行治疗。 6 天后，OCT 将血清 Ca 升高至 10.7 ± 0.21 mg/dl，对照值为 8.58 ± 0.29 mg/dl。因此，即使使用不可抑制的 PTH 源维持正常血钙条件，OCT 也具有血钙活性。这些数据表明 OCT 具有降钙活性，主要在骨骼中，但其对 PTH 的抑制作用掩盖了这一活性。然而，与 1,25-(OH)2D3 相比，OCT 的内在钙活性要低得多，但其对 PTH 分泌的影响相似。因此，OCT可能是治疗慢性肾功能衰竭继发性甲状旁腺功能亢进症的理想选择。
We previously showed that OCT, an analog of 1,25‐(OH)2D3with little calcemic activity, can decrease PTH mRNA levels in normal rats and inhibit PTH secretion in cultured bovine parathyroid cells with the same potency as 1,25‐(OH)2D3and that in normal rats fed a normal calcium diet, administration of OCT (500 ng) for 5 days did not increase plasma Ca. Thus, to determine if PTH suppression by OCT contributes to its lack of calcemic activity and to further characterize the effects of OCT on Ca metabolism, we performed several studies in parathyroidectomized (PTX) rats. PTX rats, maintained on a normal diet (0.9% Ca), received daily injections of vehicle, 1,25‐(OH)2D3(200 ng/day), or OCT (200 ng/day) for 6 days. Plasma Ca was measured daily. Plasma Ca in control rats stayed between 6.60 and 7.40 mg/dl, whereas Ca increased to 12.9 ± 0.42 mg/dl in 1,25‐(OH)2D3‐treated rats and to 9.53 ± 0.35 mg/dl in OCT‐treated rats after 6 days. With a Ca‐deficient diet, control rats maintained a plasma Ca between 4.25 and 4.60 mg/dl, but Ca increased to 13.7 ± 0.24 mg/dl with 1,25‐(OH)2D3and to 7.29 ± 0.17 mg/dl with OCT. Since the elevation in Ca by OCT was similar with both diets, OCT appears to act primarily on bone. PTX rats were infused with PTH (1.84 μg/kg/day) via an Alzet pump to achieve normal plasma Ca and then treated daily with either vehicle or OCT (200 ng/day). After 6 days, OCT increased serum Ca to 10.7 ± 0.21 mg/dl over a control value of 8.58 ± 0.29 mg/dl. Thus, even when normocalcemic conditions were maintained with a nonsuppressible source of PTH, OCT had calcemic activity. These data demonstrate that OCT has calcemic activity, mainly in the bone, that is masked by its suppressive action on PTH. When compared to 1,25‐(OH)2D3, however, the intrinsic calcemic activity of OCT is much less but its effects on PTH secretion are similar. Thus, OCT may be ideal for the treatment of the secondary hyperparathyroidism of chronic renal failure.