Nakajima Kishiko, Nohtomi Kyoko, Sato Masayo, Takano Kazue, Sato Kanji
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical University, Kawada-cho 8-1, Shinjuku-ku, Tokyo 162-8666, Japan.
Biochem Biophys Res Commun. 2009 Apr 3;381(2):283-7. doi: 10.1016/j.bbrc.2009.02.023. Epub 2009 Feb 11.
To elucidate whether PTH(7-84), a degradation product of PTH(1-84), which inhibits PTH(1-84)-induced bone resorption, also exerts an antagonistic effect on the kidney, we studied the effect of PTH(7-84) on PTH(1-34)-induced production of 1,25-(OH)2D3 in primary cultured murine renal tubules. Neonatal mouse renal tubules cultured in serum-free MEM for 7 days were treated with PTH(1-34) and/or PTH(7-84). Three hours after addition of 25-OHD(3) (10(-6) M), 1,25-(OH)2D3 was determined. PTH(1-34) stimulated the conversion of 25-OHD3 to 1,25-(OH)2D3, and PTH(7-84) dose-dependently inhibited this process. Real-time PCR revealed that PTH(1-34) increased the expression level of 1alpha-hydroxylase mRNA, whereas PTH(7-84) did not affect the expression level 1alpha or 24-hydroxylase mRNA. These in vitro data suggest that PTH(7-84) elicits an antagonistic effect in renal tubules through receptors different from the type I PTH/PTHrP receptor. This may at least partly account for the decreased serum level of 1,25-(OH)2D in patients with severe primary hyperparathyroidism with renal failure.
为了阐明甲状旁腺激素（1-84）的降解产物甲状旁腺激素（7-84）是否也对肾脏产生拮抗作用，甲状旁腺激素（7-84）可抑制甲状旁腺激素（1-84）诱导的骨吸收，我们研究了甲状旁腺激素（7-84）对原代培养的小鼠肾小管中甲状旁腺激素（1-34）诱导的1,25-二羟维生素D3生成的影响。将新生小鼠肾小管在无血清的MEM中培养7天，然后用甲状旁腺激素（1-34）和/或甲状旁腺激素（7-84）处理。加入25-羟维生素D3（10^-6 M）3小时后，测定1,25-二羟维生素D3。甲状旁腺激素（1-34）刺激25-羟维生素D3转化为1,25-二羟维生素D3，而甲状旁腺激素（7-84）呈剂量依赖性地抑制这一过程。实时PCR显示，甲状旁腺激素（1-34）增加了1α-羟化酶mRNA的表达水平，而甲状旁腺激素（7-84）不影响1α或24-羟化酶mRNA的表达水平。这些体外数据表明，甲状旁腺激素（7-84）通过与I型甲状旁腺激素/甲状旁腺激素相关蛋白受体不同的受体在肾小管中发挥拮抗作用。这可能至少部分解释了严重原发性甲状旁腺功能亢进合并肾衰竭患者血清1,25-二羟维生素D水平降低的原因。
