Nishimura A, Shinki T, Jin C H, Ohyama Y, Noshiro M, Okuda K, Suda T
Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
Endocrinology. 1994 Apr;134(4):1794-9. doi: 10.1210/endo.134.4.8137744.
We have reported that PTH inhibits 25-hydroxyvitamin D3-24-hydroxylase messenger RNA (mRNA) expression induced by 1 alpha,25-dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3] in rat kidney but not intestine. In the present study, we examined whether the suppression of 24-hydroxylase mRNA expression by PTH occurs commonly in tissues and cells which have PTH receptors. Administration of 1 alpha, 25-(OH)2D3 into rats fed a synthetic vitamin D-repleted diet containing adequate calcium greatly increased serum levels of calcium and 1 alpha, 25-(OH)2D3. Also, there was a 4-fold increase in bone 24-hydroxylase activity in response to 1 alpha, 25-(OH)2D3 administration. In rats fed a low calcium diet, renal 24-hydroxylase activity was suppressed probably due to secondary hyperparathyroidism. In contrast, the low calcium feeding did not suppress bone 24-hydroxylase activity. The expression of 24-hydroxylase mRNA in rat osteoblastic C-26 and C-11 cells was similar and attained maximal levels 24 h after cells were incubated with 10(-8) M 1 alpha, 25-(OH)2D3. Induction of 24-hydroxylase mRNA expression by 1 alpha, 25-(OH)2D3 was much greater and earlier in immature C-26 cells than mature C-11 cells. Simultaneous addition of PTH, prostaglandin E2, or cAMP together with 1 alpha, 25-(OH)2D3 did not down-regulate mRNA expression of 24-hydroxylase induced by the vitamin in both C-26 and C-11 cells. Of the three osteoblastic cells (C-26, C-20, and C-11) examined, C-26 cells showed the least mRNA expression of vitamin D receptors, in spite of the highest expression of 24-hydroxylase mRNA. These results suggest that unlike in the kidney, bone 24-hydroxylase mRNA expression is not down-regulated by PTH despite of the presence of PTH receptors. They also suggest that the degree of the induction of 24-hydroxylase mRNA by 1 alpha, 25-(OH)2D3 is not explained simply by the vitamin D receptors content.
我们曾报道，甲状旁腺激素（PTH）可抑制1α,25-二羟维生素D3[1α,25-(OH)2D3]诱导的大鼠肾脏而非肠道中的25-羟维生素D3-24-羟化酶信使核糖核酸（mRNA）表达。在本研究中，我们检测了PTH对24-羟化酶mRNA表达的抑制作用是否在具有PTH受体的组织和细胞中普遍存在。给喂食含充足钙的合成维生素D充足饮食的大鼠注射1α,25-(OH)2D3，可显著提高血清钙和1α,25-(OH)2D3水平。此外，注射1α,25-(OH)2D3后，骨24-羟化酶活性增加了4倍。给喂食低钙饮食的大鼠注射1α,25-(OH)2D3，肾脏24-羟化酶活性可能因继发性甲状旁腺功能亢进而受到抑制。相比之下，低钙饮食并未抑制骨24-羟化酶活性。大鼠成骨细胞C-26和C-11细胞中24-羟化酶mRNA的表达相似，在用10^(-8)M 1α,25-(OH)2D3孵育细胞24小时后达到最高水平。1α,25-(OH)2D3对24-羟化酶mRNA表达的诱导在未成熟的C-26细胞中比成熟的C-11细胞中更大且更早。同时添加PTH、前列腺素E2或环磷酸腺苷（cAMP）与1α,25-(OH)2D3一起，在C-26和C-11细胞中均未下调维生素诱导的24-羟化酶mRNA表达。在所检测的三种成骨细胞（C-26、C-20和C-11）中，尽管C-26细胞中24-羟化酶mRNA表达最高，但其维生素D受体的mRNA表达最少。这些结果表明，与肾脏不同，尽管存在PTH受体，但骨24-羟化酶mRNA表达不受PTH下调。它们还表明，1α,25-(OH)2D3对24-羟化酶mRNA的诱导程度不能简单地由维生素D受体含量来解释。
