Calcium-sensing receptor agonist inhibits parathyroid proliferation

Cinacalcet HCl （Cinacalcet）是一种II型拟钙化化合物，可抑制原发性和继发性甲状旁腺功能亢进患者甲状旁腺细胞的PTH分泌。在原发性甲状旁腺功能亢进症（PC2）转基因小鼠模型中，我们分析了cinacalcet对甲状旁腺细胞增殖的影响。PC2是指甲状旁腺靶向过表达cyclin D1致癌基因导致慢性生化甲状旁腺功能亢进和甲状旁腺细胞增生。将Cinacalcet （1 mg/g）加入啮齿动物的饮食中，在献祭前10天给药给80周龄PC2小鼠。与未治疗的PC2小鼠相比，cinacalcet显著抑制血清钙和PTH。与野生型小鼠相比，未经处理的PC2小鼠BrdU阳性细胞比例显著增加，并被cinacalcet显著抑制。这些数据表明，在原发性甲状旁腺功能亢进模型中，cinacalcet在体内抑制血清PTH水平和甲状旁腺细胞增殖，并可能通过抑制甲状旁腺细胞增殖来部分抑制原发性甲状旁腺功能亢进。

Cinacalcet HCl (Cinacalcet), a type II calcimimetic compound, suppresses PTH secretion from parathyroid cells in both primary and secondary hyperparathyroidism. Effect of cinacalcet on parathyroid cell proliferation was analyzed in a transgenic mouse model of primary hyperparathyroidism (PC2), in which parathyroid-targeted overexpression of the cyclin D1 oncogene causes chronic biochemical hyperparathyroidism and parathyroid cell hyperplasia. Cinacalcet was mixed into the rodent diet (1 mg/g) and orally administrated to 80 weeks-old PC2 mice for 10 days before sacrifice. Compared to untreated PC2 mice, cinacalcet significantly suppressed both serum calcium and PTH. The ratio of BrdU positive cells was significantly increased in untreated PC2 mice compared to wild type mice, and was significantly suppressed by cinacalcet. These data suggest that cinacalcet suppressed both serum PTH level and parathyroid cell proliferation in vivo in this model of primary hyperparathyroidism, and may in part suppress primary hyperparathyroidism by suppressing parathyroid cell proliferation.