title: Insulin-like growth factor receptors in normal and tumorous adult human adrenocortical glands.
abstract: We have identified and characterized insulin-like growth factor (IGF)-I and IGF-II/mannose-6-phosphate (IGF-II/M6P) receptors in normal adult human adrenocortical tissue. Furthermore, we investigated the IGF-I receptor concentration and binding characteristics in benign and carcinomatous adrenocortical tumors. Membrane preparations of 14 normal adrenocortical glands showed a mean specific 125I-IGF-I binding (SB) of 5.0 +/- 0.5% and a competition by unlabeled ligands which is characteristic of the IGF-I receptor. The Scatchard analysis revealed a single class of high affinity binding sites with a dissociation constant (Kd) of 0.16 +/- 0.03 nmol/l, and a receptor concentration (RC) of 19.2 +/- 2.5 nmol/kg protein. Affinity cross-linking experiments with normal and tumorous adrenocortical tissue displayed a band at an apparent molecular mass of 135 kDa, corresponding to the size of the normal alpha-subunit of the IGF-I receptor. In agreement, 125I-IGF-II binding to normal adult human adrenocortical membranes was characteristic for the IGF-II/M6P receptor, and the Scatchard analysis revealed the presence of a single class of high affinity binding sites (SB 7.5 +/- 0.5%, RC 1137 +/- 265 nmol/kg protein, Kd 2.20 +/- 0.46 nmol/l, n = 6). The identity of the IGF-II/M6P receptor in adrenocortical tissue was further confirmed by Western blotting showing a specific band at 220 kDa. When 125I-IGF-I binding in adrenocortical hyperplasias (SB 4.1 +/- 0.4%, RC 19.6 +/- 2.0 nmol/kg protein, Kd 0.19 +/- 0.04 nmol/l, n = 4) and adenomas (SB 4.0 +/- 1.1%, RC 17.5 +/- 3.1 nmol/kg protein, Kd 0.21 +/- 0.04 nmol/l, n = 4) was compared with the 125I-IGF-I binding in normal adrenocortical tissue, similar IGF-I receptor concentration and binding kinetics were found. In contrast, three out of four hormonally active adrenocortical carcinomas showed a strongly elevated specific 125I-IGF-I binding with a 3- to 4-fold increase in IGF-I receptor concentration, as compared with normal adrenocortical tissue. This resulted in a significantly higher mean specific binding and receptor concentration in adrenocortical carcinomas, while the binding kinetics and the size of the alpha-subunit of the IGF-I receptor remained unaltered (n = 4, SB 13.8 +/- 4.2%, RC 72.2 +/- 21.3 nmol/kg protein, Kd 0.17 +/- 0.02 nmol/l). In summary, we show that intact IGF-I and IGF-II receptors are present in normal adult human adrenocortical tissue. While the abundance of the IGF-I receptor in adrenocortical hyperplasias and adenomas was similar to normal tissue, a strong overexpression of the intact IGF-I receptor was found in three out of four adrenocortical carcinomas.
authors.affiliation: Medical Department II, Klinikum Grosshadern, University of Munich, Germany.
authors.forename: M M
authors.initials: MM
authors.lastname: Weber
authors.forename: C J
authors.initials: CJ
authors.lastname: Auernhammer
authors.forename: W
authors.initials: W
authors.lastname: Kiess
authors.forename: D
authors.initials: D
authors.lastname: Engelhardt
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000302:Adrenal Cortex / Q000378:metabolism* / Q000473:pathology; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism*; D006801:Humans; D006965:Hyperplasia; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D012016:Reference Values
chemical_list: D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1