EXPRESSION OF ADRENOCORTICOTROPIC HORMONE-RECEPTOR MESSENGER-RNA IN HUMAN ADRENOCORTICAL NEOPLASMS - CORRELATION WITH P450SCC EXPRESSION

OBJECTIVE Adrenocorticotrophin (ACTH) is the main hormone-regulating s teroid secretion from the adrenal cortex. The ACTH receptor (ACTH-R) h as recently been cloned, allowing systematic evaluation of its express ion and function in adrenal tumorigenesis. We investigated ACTH-R and P450 side-chain cleavage enzyme (P450scc) mRNA expression in a variety of neoplastic adrenocortical tissues by Northern blot and reverse-tra nscriptase-PCR (RT-PCR), PATIENTS AND MEASUREMENTS We studied tissue f rom eight normal adrenals, six diffuse adrenocortical hyperplasias in patients with ACTH-dependent Gushing's syndrome, 22 adrenal adenomas, six carcinomas and two carcinoma cell lines, Poly A mRNA was electroph oresed, immobilized on a nylon membrane and hybridized using alpha(32) P-CTP labelled human ACTH-R and P450scc cDNAs. RESULTS Mean ACTH-R mRN A expression showed significant differences between groups (P = 0.0001 ), but appeared to be independent of plasma ACTH concentrations, Compa red to normal adrenal (= 100 +/- 12%), expression was low in non-funct ional adenomas (23 +/- 11%) and carcinomas (19 +/- 12%), intermediate in adrenocortical hyperplasias (88 +/- 6%) and cortisol-producing aden omas(81 +/- 15%) and high in aldosteronomas (175 +/- 29%). In adenomas , ACTH-R mRNA expression correlated closely with the expression of P45 0scc mRNA(r = 0.8, P = 0.0001) suggesting regulation by similar factor s. However, carcinomas and cancer cell lines did not show a positive c orrelation between these two parameters (r = -0.44, P = 0.3). CONCLUSI ONS We have demonstrated that plasma ACTH is not the major factor infl uencing ACTH-receptor mRNA expression in neoplastic adrenal tissue, In benign tumours of the adrenal cortex there was a close positive corre lation between ACTH-receptor mRNA and P450scc mRNA which was missing i n adrenocortical carcinomas, probably as a result of tumour dedifferen tiation.