Almaden Y, Hernandez A, Torregrosa V, Canalejo A, Sabate L, Fernandez Cruz L, Campistol J M, Torres A, Rodriguez M
Unidad de Investigación, Servicio de Nefrologia Hospital Universitario Reina Sofia, Cordoba, Spain.
J Am Soc Nephrol. 1998 Oct;9(10):1845-52. doi: 10.1681/ASN.V9101845.
Phosphate retention plays an important role in the pathogenesis of secondary hyperparathyroidism in patients with renal failure. In in vitro studies, high extracellular phosphate levels directly stimulate PTH secretion in rat and bovine parathyroid tissue. The present study evaluates the effect of high phosphate levels on the secretion of PTH and the production of prepro PTH mRNA in human hyperplastic parathyroid glands. The study includes parathyroid glands obtained from patients with primary adenomas and from hemodialysis and kidney-transplant patients with diffuse and nodular secondary hyperplasia. The experiments were performed in vitro using small pieces of parathyroid tissue. The ability of high calcium levels to decrease PTH secretion was less in adenomas than in secondary hyperplasia; among the secondary hyperplasia, nodular was less responsive to an increase in calcium than diffuse hyperplasia. In diffuse hyperplasia, PTH secretion was increased in response to 3 and 4 mM phosphate compared with 2 mM phosphate, despite a high calcium concentration in the medium; prepro PTH mRNA levels increased after incubation in 4 mM phosphate. Similar results were obtained with nodular hyperplasia, except that the elevation of PTH secretion in response to 3 mM phosphate did not attain statistical significance. In adenomas, high calcium concentrations (1.5 mM) did not result in inhibition of PTH secretion, independent of the phosphate concentration, and the prepro PTH mRNA was not significantly increased by high phosphate levels. In conclusion, first, the PTH secretory response to an increase in calcium concentration is less in nodular than diffuse hyperplasia; second, high phosphate levels directly affect PTH secretion and gene expression in patients with advanced secondary hyperparathyroidism.
磷潴留在肾衰竭患者继发性甲状旁腺功能亢进的发病机制中起重要作用。在体外研究中，高细胞外磷水平直接刺激大鼠和牛甲状旁腺组织中的甲状旁腺激素（PTH）分泌。本研究评估高磷水平对人增生性甲状旁腺中PTH分泌及前甲状旁腺素原（prepro PTH）mRNA产生的影响。该研究纳入了来自原发性腺瘤患者以及血液透析和肾移植后弥漫性和结节性继发性增生患者的甲状旁腺。实验采用甲状旁腺组织小块在体外进行。高钙水平降低PTH分泌的能力在腺瘤中比在继发性增生中弱；在继发性增生中，结节性增生对钙增加的反应比弥漫性增生弱。在弥漫性增生中，与2 mM磷相比，3 mM和4 mM磷会使PTH分泌增加，尽管培养基中钙浓度较高；在4 mM磷中孵育后，前甲状旁腺素原mRNA水平升高。结节性增生也得到了类似结果，只是3 mM磷引起的PTH分泌升高未达到统计学显著性。在腺瘤中，高钙浓度（1.5 mM）不会抑制PTH分泌，与磷浓度无关，高磷水平也不会使前甲状旁腺素原mRNA显著增加。总之，第一，结节性增生对钙浓度增加的PTH分泌反应比弥漫性增生弱；第二，高磷水平直接影响晚期继发性甲状旁腺功能亢进患者的PTH分泌和基因表达。
