DEFECT OF RECEPTOR-CYCLASE COUPLING PROTEIN IN PSEUDOHYPOPARATHYROIDISM
DEFECT OF RECEPTOR-CYCLASE COUPLING PROTEIN IN PSEUDOHYPOPARATHYROIDISM
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DOI：
10.1056/nejm198007313030501
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发表时间：
1980-01-01
影响因子：
158.5
通讯作者：
BOURNE, HR
中科院分区：
文献类型：
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作者：
FARFEL, Z;BRICKMAN, AS;BOURNE, HR
激素敏感腺苷酸环化酶含有一种最近发现的蛋白质成分，该成分是激素和鸟嘌呤核苷酸刺激cAMP合成所必需的；该成分可能将膜受体与环化酶偶联。该蛋白（称为N）在假性甲状旁腺功能低下患者的红细胞膜中进行了研究，通过测定该蛋白的生化活性及其在[32P]NAD和霍乱毒素存在下对放射性标记的敏感性。通过两种方法，10例1型假性甲状旁腺功能减退症患者中有5例的红细胞中该蛋白的活性与正常和甲状旁腺功能减退症患者和1例11型假性甲状旁腺功能减退症患者的红细胞相比降低了40-50%。如果N蛋白的活性在其他组织中降低，这种缺乏可能导致假性甲状旁腺功能减退症的靶器官对甲状旁腺激素和其他通过cAMP起作用的激素产生抵抗。1个家族5例1型假性甲状旁腺功能低下患者红细胞N蛋白活性无缺陷；该家族的生化缺陷仍未明确。
Hormone-sensitive adenylate cyclase contains a recently discovered protein component that is required for stimulation of cAMP synthesis by hormones and guanine nucleotides; the component presumably couples the membrane receptor to the cyclase. This protein (termed N) was studied in erythrocyte membranes of patients with pseudohypoparathyroidism, using assays of the protein''s biochemical activity and of its susceptibility to radiolabeling in the presence of [32P]NAD and cholera toxin. By both assays, the protein''s activity was reduced by 40-50% in erythrocytes of 5 of 10 patients with Type 1 pseudohypoparathyroidism as compared with those of normal and hypoparathyroid subjects and 1 patient with Type 11 pseudohypoparathyroidism. If activity of the N protein is reduced in other tissues, this deficiency could cause the resistance of target organs in pseudohypoparathyroidism to parathyroid hormone and other hormones that work via cAMP. Erythrocytes of 5 patients with Type 1 pseudohypoparathyroidism, all in 1 family, showed no defect in activity of the N protein; the biochemical defect of this family remains undefined.