4-PARAMETER MODEL OF THE SIGMOIDAL RELATIONSHIP BETWEEN PARATHYROID-HORMONE RELEASE AND EXTRACELLULAR CALCIUM-CONCENTRATION IN NORMAL AND ABNORMAL PARATHYROID TISSUE

4-PARAMETER MODEL OF THE SIGMOIDAL RELATIONSHIP BETWEEN PARATHYROID-HORMONE RELEASE AND EXTRACELLULAR CALCIUM-CONCENTRATION IN NORMAL AND ABNORMAL PARATHYROID TISSUE
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DOI:
10.1210/jcem-56-3-572
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发表时间:
1983-01-01
影响因子:
5.8
通讯作者:
BROWN, EM
BROWN, EM
中科院分区:
医学2区
文献类型:
--
作者:
BROWN, EM

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一个计算机程序被用来曲线拟合数据相关的PTH [甲状旁腺激素]释放在体外的细胞外钙浓度的甲状旁腺细胞从正常牛和人类以及病理人类甲状旁腺组织制备。在牛细胞和82%的人细胞制剂中,PTH释放超过50%的抑制高钙浓度,数据成功地拟合对称的S形曲线。这些曲线由4个参数定义[A =最大PTH释放,B =设定点处的曲线斜率,C =设定点(引起分泌的半最大抑制的Ca浓度),和D =最小PTH释放]。这些参数的预测值和以前使用视觉拟合得到的预测值之间有很好的一致性。还生成了程序的理论曲线,以评估参数A至D的变化对甲状旁腺功能亢进患者PTH分泌过多的可能贡献。这些分析表明,最大PTH分泌,曲线的斜率,设定点和最大抑制PTH释放的变化都可能有助于激素分泌过多。然而,在定量的基础上,在设定点的变化产生了最大的变化,在分泌率为一个给定的参数值的变化。这些结果为PTH释放与细胞外Ca浓度之间的关系提供了数学模型。此外,他们提供了一种手段,从理论上分析的各种质的变化,在这种关系的状态下,低和高分泌的甲状旁腺素的贡献。
A computer program was employed to curve-fit data relating PTH [parathyroid hormone] release in vitro to the extracellular Ca concentration in parathyroid cells prepared from normal bovine and human as well as pathological human parathyroid tissue. In bovine cells and 82% of human cell preparations in which PTH release was more than 50% suppressible by high Ca concentrations, the data were successfully fitted to symmetrical sigmoidal curves. Such curves were defined by 4 parameters [A = maximum PTH release, B = slope of the curve at the set-point, C = set-point (Ca concentration causing half-maximal inhibition of secretion), and D = minimum PTH release]. There was excellent agreement between the predicted values for these parameters and those obtained previously using visual fits. Theoretical curves with the program were also generated to assess the possible contribution of changes in parameters A through D to hypersecretion of PTH in hyperparathyroidism. These analyses suggested that changes in maximal PTH secretion, slope of the curve, set-point and maximal suppressibility of PTH release all might contribute to hormonal hypersecretion. On a quantitative basis, however, changes in the set-point produced the largest alteration in secretory rate for a given change in the value of a parameter. These results provide a mathematical model for the relationship between PTH release and the extracellular Ca concentration. Moreover, they provide a means of analyzing theoretically the contribution of various qualitative changes in this relationship to states of hypo- and hypersecretion of PTH.