{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T16:22:34Z","timestamp":1760977354981,"version":"3.30.1"},"reference-count":37,"publisher":"Wiley","issue":"s3","license":[{"start":{"date-parts":[[2002,1,4]],"date-time":"2002-01-04T00:00:00Z","timestamp":1010102400000},"content-version":"vor","delay-in-days":399,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2000,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The insulin\u2010like growth factor (IGF) system plays a central role in the mechanism of transformation and tumourigenesis. Elevated levels of IGF\u2010II and IGF\u2010I have been found in adrenocortical carcinomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>We examined binding characteristics and concentrations of both IGF\u2010receptors in normal adult human adrenocortical glands, and compared them with the IGF\u2010I receptor binding in adrenocortical tumours of various origins. The human IGF\u2010I receptor was overexpressed in the mouse adrenocortical tumour cell line Y1, and growth studied in response to IGF stimulation. The influence of IGF\u2010II on adrenal morphology and function was assessed in transgenic mice that postnatally overexpress IGF\u2010II.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>While the abundance of the IGF\u2010I receptor in adrenocortical hyperplasias and adenomas was similar to normal tissue, a strong overexpression of the intact IGF\u2010I receptor was found in three out of four adrenocortical carcinomas. Y1 cells overexpressing the human IGF\u2010I receptor respond to IGF\u2010I with an increase in thymidine incorporation by 140%. Furthermore, the antiproliferative effect of ACTH is blunted. In transgenic mice postnatally overexpressing IGF\u2010II, adrenal weight is increased, mainly due to a 50% increase in the number of zona fasciculata cells. Plasma corticosterone levels in these mice are twofold higher than in controls, in contrast to similar plasma ACTH levels, thus indicating a direct effect of IGF\u2010II on adrenal cell hyperplasia and function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>There is substantial evidence that the IGF\u2010system is involved in adrenal growth and tumourigenesis. High local levels of IGF\u2010II in combination with elevated IGF\u2010I receptor concentrations would represent a significant growth advantage of the adrenocortical carcinoma cell and could contribute to a highly malignant phenotype. IGF\u2010II overexpression alone seems not to be sufficient for malignant transformation.<\/jats:p><\/jats:sec>","DOI":"10.1046\/j.1365-2362.2000.0300s3069.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T15:50:05Z","timestamp":1047397805000},"page":"69-75","source":"Crossref","is-referenced-by-count":30,"title":["The role of the insulin\u2010like growth factor system in adrenocortical tumourigenesis"],"prefix":"10.1111","volume":"30","author":[{"given":"M. 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