Silve C, Suarez F, el Hessni A, Loiseau A, Graulet A M, Gueris J
Laboratoire du Calcium et Tissu Osseux dans l'Organisme en Developpement, CNRS URA 583, Paris, France.
J Clin Endocrinol Metab. 1990 Sep;71(3):631-8. doi: 10.1210/jcem-71-3-631.
Skin fibroblasts from some patients with pseudohypoparathyroidism type Ib (PHP-Ib) are resistant to PTH. To characterize the defect producing PTH resistance in these cells and determine whether the abnormality is potentially reversible, we evaluated the ability of fibroblasts from patients with PHP-Ib to produce cAMP in response to PTH both before and after exposure to dexamethasone, an agent known to increase PTH responsiveness in other cell types. Before dexamethasone treatment, fibroblasts from five of eight patients with PTH-Ib produced reduced amounts of cAMP in response to PTH (but not prostaglandin E1 and forskolin) compared to that of control cells (6.3 +/- 1.0 and 37.3 +/- 6.3 pmol cAMP/100 micrograms protein, respectively). Whereas dexamethasone pretreatment had no effect on cAMP production by control or PTH-responsive PHP-Ib fibroblasts, it resulted in a dose-dependent increase in PTH-induced cAMP production by PTH-resistant fibroblasts to normal levels in four of five cases. Studies evaluating the binding of radiolabeled PTH did not permit quantification of the small number of high affinity PTH receptors present on these cells. We conclude that PTH resistance in PHP-Ib patients with PTH-resistant fibroblasts results from an abnormality in the expression of or coupling to cyclase of high affinity PTH-receptor complexes. Because it is expressed in only some tissues and is reversible, the defect could be regulatory in nature.
一些I b型假性甲状旁腺功能减退症（PHP-Ib）患者的皮肤成纤维细胞对甲状旁腺激素（PTH）具有抗性。为了明确导致这些细胞产生PTH抗性的缺陷，并确定该异常是否具有潜在的可逆性，我们评估了PHP-Ib患者的成纤维细胞在暴露于地塞米松前后对PTH产生环磷酸腺苷（cAMP）的能力，地塞米松是一种已知可增加其他细胞类型对PTH反应性的药物。在地塞米松治疗前，与对照细胞相比，8例PTH-Ib患者中有5例的成纤维细胞对PTH（而非前列腺素E1和福斯高林）产生的cAMP量减少（分别为6.3±1.0和37.3±6.3 pmol cAMP/100微克蛋白质）。虽然地塞米松预处理对对照或对PTH有反应的PHP-Ib成纤维细胞产生cAMP没有影响，但在5例中有4例导致对PTH有抗性的成纤维细胞中PTH诱导的cAMP产生呈剂量依赖性增加至正常水平。评估放射性标记PTH结合的研究无法对这些细胞上存在的少量高亲和力PTH受体进行定量。我们得出结论，具有PTH抗性成纤维细胞的PHP-Ib患者中的PTH抗性是由高亲和力PTH受体复合物与环化酶的表达或偶联异常所致。由于该缺陷仅在某些组织中表达且是可逆的，其本质可能是调节性的。
