Deftos L J, Hogue-Angeletti R, Chalberg C, Tu S
Department of Medicine (Endocrine Division), University of California, San Diego.
Endocrinology. 1989 Jul;125(1):563-5. doi: 10.1210/endo-125-1-563.
We studied the regulation of the secretion in vitro of the parathyroid hormone-related protein (PTHrP) associated with the hypercalcemia of malignancy by Chromogranin A (CgA)-derived peptides and by human calcitonin (CT) in the BEN human lung tumor cell line. The amino terminal peptide of CgA, CgA1-40, inhibited the secretion of PTHrP, whereas other peptides had no such effect. Human CT stimulated the secretion of PTHrP, whereas other hormones had no such effect. Both effects occurred in a dose-dependent manner. These studies reveal novel regulatory pathways among peptides and proteins that are commonly associated with each other and can have paracrine interactions. CgA may be processed at its multiple dibasic sites to peptides that regulate the secretion of its co-resident hormones, in this case PTHrP. In addition to a paracrine effect, CT may be clinically useful as a provocative agent for PTHrP secretion. Complex interactions are present among the calcium-regulating hormones and their associated proteins.
我们在BEN人肺癌细胞系中研究了嗜铬粒蛋白A（CgA）衍生肽和人降钙素（CT）对与恶性肿瘤高钙血症相关的甲状旁腺激素相关蛋白（PTHrP）体外分泌的调节作用。CgA的氨基末端肽CgA1-40可抑制PTHrP的分泌，而其他肽则无此作用。人CT可刺激PTHrP的分泌，而其他激素则无此作用。两种作用均呈剂量依赖性。这些研究揭示了通常相互关联且可发生旁分泌相互作用的肽和蛋白质之间新的调节途径。CgA可能在其多个双碱性位点被加工成调节其共存激素（在本案例中为PTHrP）分泌的肽。除了旁分泌作用外，CT在临床上可能可用作刺激PTHrP分泌的激发剂。钙调节激素及其相关蛋白之间存在复杂的相互作用。
