Yamamoto M, Igarashi T, Muramatsu M, Fukagawa M, Motokura T, Ogata E
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
J Clin Invest. 1989 Mar;83(3):1053-6. doi: 10.1172/JCI113946.
To examine the effects of serum calcium concentrations on PTH biosynthesis, rats were made hyper- (serum total calcium, approximately 3.5 mM) or hypocalcemic (approximately 1.25 mM) and steady-state levels of PTH mRNA in parathyroid cells were measured by the primer extension method using a 32P-labeled synthetic oligomer. PTH mRNA levels increased about twofold in the rats made slightly hypocalcemic by infusion of calcium-free solution and decreased slightly in those made hypercalcemic by CaCl2 infusion (120-150 mumol/h) compared with the levels present in nonfasting control rats. Infusion of calcitonin (0.5 U/h) or EGTA (90 mumol/h) with calcium-free solution increased PTH mRNA levels further (two- to sevenfold) above the levels present in animals infused with calcium-free solution alone. These changes in PTH mRNA levels were observed after 48- but not 24-h infusion, and there was an inverse correlation between PTH mRNA levels and serum calcium concentrations. The results suggest that changes in serum calcium concentrations in the near physiological range regulate the biosynthesis of PTH by affecting steady-state levels of PTH mRNA when hypercalcemia or hypocalcemia continues for a relatively long period.
为研究血清钙浓度对甲状旁腺激素(PTH)生物合成的影响,将大鼠制成高钙血症(血清总钙约3.5 mM)或低钙血症(约1.25 mM),并采用32P标记的合成寡聚体通过引物延伸法测量甲状旁腺细胞中PTH mRNA的稳态水平。与非禁食对照大鼠相比,通过输注无钙溶液使大鼠轻度低钙血症时,PTH mRNA水平增加约两倍;通过氯化钙输注(120 - 150 μmol/h)使大鼠高钙血症时,PTH mRNA水平略有下降。与仅输注无钙溶液的动物相比,在无钙溶液中输注降钙素(0.5 U/h)或乙二醇双四乙酸(EGTA,90 μmol/h)可使PTH mRNA水平进一步升高(两到七倍)。这些PTH mRNA水平的变化在输注48小时后而非24小时后观察到,且PTH mRNA水平与血清钙浓度呈负相关。结果表明,当高钙血症或低钙血症持续较长时间时,接近生理范围的血清钙浓度变化通过影响PTH mRNA的稳态水平来调节PTH的生物合成。