LOCALIZATION AND EXPRESSION OF ADRENOCORTICOTROPIC HORMONE-RECEPTOR MESSENGER-RNA IN NORMAL AND NEOPLASTIC HUMAN ADRENAL-CORTEX

The recent cloning of the ACTH receptor (ACTH-R) gene allows investiga tion of the tissue localization and relative abundance of ACTH-R mRNA in normal and neoplastic adrenal cortex. Using in situ hybridization ( ISH) we studied the expression of ACTH-R mRNA in four adult adrenals o f brain-dead patients, two cortisol-producing adenomas (CPA), three al dosterone-producing adenomas (APA), one non-functional adenoma (NFA), and three cat-cinemas. The results were compared with the mRNA express ion of key steroidogenic enzymes and of the glucocorticoid receptor (G R) mRNA using Northern blotting. In adult adrenals, messenger RNA enco ding ACTH-R was localized in all three zones of the adrenal cortex, in accordance with the stimulatory role of ACTH on mineralocorticoid, gl ucocorticoid and adrenal androgen secretion. In comparison, expression of side-chain cleavage enzyme (P450scc) showed a similar tissue distr ibution with mRNA abundance in all three zones, whereas 17-hydroxylase /17-20 lyase (P450c17) mRNA expression was only detected in the zona f asciculata and zona reticularis. All CPAs and APAs expressed significa nt levels of ACTH-R mRNA whereas an NFA showed low expression of ACTH- II mRNA. Two of three adrenocortical carcinomas expressed ACTH-R mRNA. Northern analysis using dot blot was employed to quantify ACTH-R and GR mRNA expression and confirmed the ISH data: ACTH-R mRNA expression was high in CPAs (275 and 195% iis 100 +/- 25% in adult adrenals), APA s (127, 200 and 221%) and two carcinomas (99 and 132%), but low in the NFA (7%) and in an androgen secreting carcinoma (16%). GR mRNA expres sion was high in the NFA (195%) and in two of three carcinomas (93, 18 8, 227%). We conclude that ACTH-R mRNA is up-regulated in functional a denomas by yet unidentified mechanisms. The tissue distribution of ACT H-R and P450 enzyme mRNA expression is highly variable in neoplastic a drenals and does not allow a clear differentiation between benign and malignant tumors.