INSULIN-LIKE GROWTH-FACTOR-I RECEPTORS AND INSULIN-LIKE GROWTH FACTOR-BINDING PROTEINS IN HUMAN PARATHYROID TUMORS

Studies have demonstrated the presence of epidermal growth factor rece ptors in human parathyroid tumors. However, there is little informatio n on the effect of other peptide growth factors on parathyroid cell gr owth. We therefore studied the interaction of insulin-like growth fact or T (IGF-I) with human parathyroid tumor cells. Parathyroid tissues w ere obtained from 24 patients with primary or secondary hyperparathyro idism. There were 15 solitary adenomas, 5 carcinomas, and 4 hyperplast ic tissues. First, the binding of [I-125]IGF-I to the crude membrane f ractions was studied by competitive inhibition with unlabeled IGF-I. S econd, isolated parathyroid cells were cultured with IGF-I and examine d for DNA synthesis. The IGF-binding protein (IGFBP) content of tissue homogenates was determined by ligand blot analysis. The binding of [I -125]IGF-I to parathyroid membranes was dependent on time, temperature , and pH of the medium. Maximum binding was obtained after incubation for 18 hours at 4 degrees C. Specific binding to parathyroid cancer me mbranes (mean +/- SE, 10.75 +/- 10.55%/mg protein) was significantly ( p < 0.05) greater than that in adenoma tissues (3.71 +/- 2.11%/mg). Th e value in hyperplastic tissues (4.78 +/- 2.97%/mg) was not different from that in adenomas. Affinity cross-linking and autoradiography demo nstrated the type I IGF receptors. Cultured parathyroid cells responde d to IGF-I with increased DNA synthesis. The parathyroid tumor tissues expressed IGFBPs. These results suggest that IGF-I and IGFBPs are inv olved in the growth regulation of parathyroid tumor cells.