EXPRESSION OF INSULIN-LIKE-GROWTH-FACTOR BINDING-PROTEIN 1-6 GENES INADRENOCORTICAL TUMORS AND PHEOCHROMOCYTOMAS

The insulin-like growth factor (IGF) system appears to be important in the regulation of adrenal growth and hormone synthesis. As IGF-bindin g proteins (IGFBPs) modify IGF bioactivity, we investigated the expres sion of IGFBP 1-6 genes in different adrenal tumors and hyperplasias t o further clarify the role of the IGF system in adrenal pathophysiolog y. IGFBP-1 mRNA levels were tao low to be detected by Northern blot an alysis, but could be found by RI-PCR in some tumors and hyperplastic a drenals. Other IGFBPs were detected by Northern blotting. IGFBP-3 mRNA levels were very low in normal adrenals, In adrenal tumors and hyperp lastic adrenals, IGFBP-3 mRNA expression was usually higher than in no rmal adrenals. In hormonally active adrenocortical carcinomas, IGFBP-2 , -4, -5 and -6 mRNA levels were lower than in nonfunctional carcinoma s and normal adrenals. The low IGFBP mRNA expression in the hormone-pr oducing carcinomas was associated with high ICF-II mRNA content. In ad renocortical adenomas from patients with Gushing's or Conn's syndrome, mean IGFBP mRNA levels were higher than in normal adrenals or in horm onally inactive adenomas. In nodular and bilateral hyperplasias, IGFBP -2, -3 and -4 mRNA expression was on average higher than in normal adr enals but varied substantially, as did IGFBP mRNA levels in pheochromo cytomas. In comparison to normal adrenals, pheochromocytomas expressed on average higher levels of IGFBP-2 and -4 but less IGFBP-5 and -6 mR NAs. Our data show that the six IGFBPs 1-6 are expressed at variable l evel in adrenal tumors and hyperplasias. The low level of IGFBP mRNAs in hormonally active adrenocortical carcinomas was of particular inter est.