Tian J, Smogorzewski M, Kedes L, Massry S G
Department of Medicine, University of Southern California School of Medicine, Los Angeles.
Am J Nephrol. 1994;14(1):41-6. doi: 10.1159/000168684.
Resistance to the action of PTH is encountered in chronic renal failure (CRF). This was attributed to downregulation of PTH receptor due to the state of secondary hyperparathyroidism of CRF. The present study examined whether the amount of PTH-PTH-related peptide (PTH-PTHrP) mRNA in a traditional (kidney) and a nontraditional (liver) organs for PTH action was reduced in CRF. PTH-PTHrP mRNA was measured in kidney and liver obtained from normal rats, animals with CRF of 6 weeks' duration, normocalcemic parathyroidectomized CFR rats and from CRF and normal rats treated with verapamil. The mRNA of receptor was quantitated with Northern blot analysis of kidney RNA and liver poly A+ RNA. The relative amounts of mRNA of the PTH-PTHrP receptor to that of beta-actin in both kidney and liver of CRF rats were significantly (p < 0.01) lower than in normal animals. Parathyroidectomy of CRF rats was followed either by significant (p < 0.01) improvement (kidney) or normalization (liver) of the receptor mRNA. Treatment of CRF rats with verapamil also significantly (p < 0.01) improved the concentration of the receptor mRNA in the kidney. The data demonstrate that CRF is associated with downregulation of the PTH-PTHrP receptor mRNA in kidney and liver. This defect is partially or completely reversed by parathyroidectomy of the CRF rats or their treatment with verapamil. The decrease in the receptor mRNA would likely result in a decrease in PTH receptor synthesis and consequently PTH receptor numbers, and hence relative resistance to the action of PTH.(ABSTRACT TRUNCATED AT 250 WORDS)
慢性肾衰竭（CRF）时会出现对甲状旁腺激素（PTH）作用的抵抗。这归因于CRF继发性甲状旁腺功能亢进状态导致的PTH受体下调。本研究检测了CRF时，PTH作用的传统（肾脏）和非传统（肝脏）器官中PTH-甲状旁腺激素相关肽（PTH-PTHrP）mRNA的量是否减少。在从正常大鼠、病程6周的CRF动物、血钙正常的甲状旁腺切除的CFR大鼠以及用维拉帕米治疗的CRF和正常大鼠获取的肾脏和肝脏中测量PTH-PTHrP mRNA。用肾脏RNA和肝脏多聚腺苷酸+RNA的Northern印迹分析对受体mRNA进行定量。CRF大鼠肾脏和肝脏中PTH-PTHrP受体mRNA与β-肌动蛋白mRNA的相对量显著低于正常动物（p<0.01）。CRF大鼠甲状旁腺切除后，受体mRNA显著改善（肾脏，p<0.01）或恢复正常（肝脏）。用维拉帕米治疗CRF大鼠也显著改善了肾脏中受体mRNA的浓度（p<0.01）。数据表明，CRF与肾脏和肝脏中PTH-PTHrP受体mRNA下调有关。CRF大鼠甲状旁腺切除或用维拉帕米治疗可部分或完全逆转这一缺陷。受体mRNA的减少可能导致PTH受体合成减少，进而导致PTH受体数量减少，并因此导致对PTH作用的相对抵抗。（摘要截短于250字）
