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Insulin-like growth factor I receptors and insulin-like growth factor-binding proteins in human parathyroid tumors

✍ Scribed by Reiko Tanaka; Toshio Tsushima; Hitomi Murakami; Kazuo Shizume; Takao Obara


Publisher
Springer
Year
1994
Tongue
English
Weight
921 KB
Volume
18
Category
Article
ISSN
0364-2313

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✦ Synopsis


Studies have demonstrated the presence of epidermal growth

factor receptors in human parathyroid tumors. However, there is little information on the effect of other peptide growth factors on parathyroid cell growth. We therefore studied the interaction of insulin-like growth factor I (IGF-I) with human parathyroid tumor cells. Parathyroid tissues were obtained from 24 patients with primary or secondary hyperparathyroidism. There were 15 solitary adenomas, 5 carcinomas, and 4 hyperplastic tissues. First, the binding of [12sI]IGF-I to the crude membrane fractions was studied by competitive inhibition with unlabeled IGF-I. Second, isolated parathyroid cells were cultured with IGF-I and examined for DNA synthesis. The IGF-binding protein (IGFBP) content of tissue homogenates was determined by ligand blot analysis. The binding of [12sI]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"C. Specific binding to parathyroid cancer membraneS (mean -+ SE, 10.75 + 10.55%/mg protein)was significantly (p < 0.05) greater than that in adenoma tissues (3.71 -+ 2.11%/mg). The value in hyperplastic tissues (4.78 -+ 2.97 %/mg) was not different from that in adenomas. Affinity cross-linking and autoradiography demonstrated the type I IGF receptors. Cultured parathyroid cells responded to IGF-I with increased DNA synthesis. The parathyroid tumor tissues expressed IGFBPs. These results suggest that IGF-I and IGFBPs are involved in the growth regulation of parathyroid tumor cells.

Hyperparathyroidism is caused by parathyroid adenoma, hyperplasia, or carcinoma of parathyroid cells. The factors responsible for the uncontrolled growth of parathyroid cells are, however, poorly understood [1][2][3]. One study revealed epidermal growth factor receptors in human parathyroid tumors [4], suggesting that this growth factor may be involved in the growth of parathyroid cells. However, there is little information on the receptors for other peptide growth factors on parathyroid cells.

Insulin-like growth factors (IGFs) are a class of growth hormone (GH)-dependent growth factors that are structurally related to proinsulin [5,6]. Two types of IGF have been identified. It is well established that most of the growthpromoting activity of GH is mediated by . Both


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