Chertow B S, Baylink D J, Wergedal J E, Su M H, Norman A W
J Clin Invest. 1975 Sep;56(3):668-78. doi: 10.1172/JCI108137.
The present study determined the effects of 1,25-dihydroxycholecalciferol on serum immunoactive parathyroid hormone and on parathyroid hormone secretion in vitro. Rats injected i.p. with 1,25-dihydroxycholecalciferol, 130 pmol (2 U)/140 g body wt, which is probably a physiologic dose, had a significant 43% decrease in serum immunoreactive parathyroid hormone at 4 h. In addition, this dose of 1,25-dihydroxycholecalciferol inhibited the serum immunoreactive parathyroid hormone response to hypocalcemia induced by phosphate injection. Because the increment in serum immunoreactive parathyroid hormone was less but the decrement in serum calcium more in phosphate plus 1,25-dihydroxycholecalciferol-treated than in phosphate plus vehicle-treated rats, the impaired serum immunoreactive parathyroid hormone response to 1,25-dihydroxycholecalciferol could not be attributed to the change in serum calcium. In studies of parathyroid hormone secretion from bovine parathyroid tissue in vitro, the concentration of 1,25-dihydroxycholecalciferol used for most experiments was 1nM, which is in the range found in rat serum. 1,25-Dihydroxycholecalciferol at 1 or 100 nM significantly inhibited parathyroid hormone secretion when medium calcium concentration was normal (1.5 mM), high (3.0 mM), and low (1.0 mM). Maximum inhibition ranged from 19 to 74%; inhibition was generally seen after 2 h of incubation; and inhibition was sustained or progressive thereafter. Vitamin A, 0.1 muM, caused a marked stimulation of parathyroid hormone secretion. 1,25-Dihydroxycholecalciferol at 1 nM markedly reduced (44%) the effect of vitamin A to stimulate parathyroid hormone secretion. This effect of 1,25-dihydroxycholecalciferol was maximal at 1 h and persisted thereafter. Another steroid, hydrocortisone, 10 muM, did not inhibit parathyroid hormone secretion, suggesting that the 1,25-dihydroxycholecalciferol effect was not a nonspecific inhibitory effect on parathyroid cells. Because other workers have shown that parathyroid hormone directly stimulates 1,25-dihydroxycholecalciferol secretion, our results are consistent with the concept that there is a feedback loop where parathyroid hormone directly stimulates secretion of 1,25-dihydroxycholecalciferol, which in turn directly inhibits secretion of parathyroid hormone.
本研究测定了1,25 - 二羟胆钙化醇对血清免疫活性甲状旁腺激素及甲状旁腺激素体外分泌的影响。腹腔注射1,25 - 二羟胆钙化醇（130 pmol，即2 U/140 g体重，这可能是生理剂量）的大鼠，在4小时时血清免疫反应性甲状旁腺激素显著降低了43%。此外，该剂量的1,25 - 二羟胆钙化醇抑制了血清免疫反应性甲状旁腺激素对注射磷酸盐诱导的低钙血症的反应。因为与注射磷酸盐加赋形剂的大鼠相比，注射磷酸盐加1,25 - 二羟胆钙化醇的大鼠血清免疫反应性甲状旁腺激素的增加较少，但血清钙的降低较多，所以血清免疫反应性甲状旁腺激素对1,25 - 二羟胆钙化醇反应受损不能归因于血清钙的变化。在体外对牛甲状旁腺组织甲状旁腺激素分泌的研究中，大多数实验所用的1,25 - 二羟胆钙化醇浓度为1 nM，这在大鼠血清中发现的范围内。当培养基钙浓度正常（1.5 mM）、高（3.0 mM）和低（1.0 mM）时，1 nM或100 nM的1,25 - 二羟胆钙化醇显著抑制甲状旁腺激素分泌。最大抑制率在19%至74%之间；一般在孵育2小时后出现抑制；此后抑制持续或进展。0.1 μM的维生素A引起甲状旁腺激素分泌的显著刺激。1 nM的1,25 - 二羟胆钙化醇显著降低（44%）维生素A刺激甲状旁腺激素分泌的作用。1,25 - 二羟胆钙化醇的这种作用在1小时时最大，此后持续存在。另一种类固醇，10 μM的氢化可的松，不抑制甲状旁腺激素分泌，这表明1,25 - 二羟胆钙化醇的作用不是对甲状旁腺细胞的非特异性抑制作用。因为其他研究人员已经表明甲状旁腺激素直接刺激1,25 - 二羟胆钙化醇分泌，我们的结果与以下概念一致，即存在一个反馈回路，其中甲状旁腺激素直接刺激1,25 - 二羟胆钙化醇的分泌，而1,25 - 二羟胆钙化醇又反过来直接抑制甲状旁腺激素的分泌。
