Expression of adrenocorticotrophic hormone receptor mRNA in human adrenocortical neoplasms: correlation with P450scc expression

OBJECTIVEAdrenocorticotrophin (ACTH) is the main hormone‐regulating steroid secretion from the adrenal cortex. The ACTH receptor (ACTH‐R) has recently been cloned, allowing systematic evaluation of its expression 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‐transcriptase‐PCR (RT‐PCR). PATIENTS AND MEASUREMENTSWe studied tissue from eight normal adrenals, six diffuse adrenocortical hyperplasias in patients with ACTH‐dependent Cushing's syndrome, 22 adrenal adenomas, six carcinomas and two carcinoma cell lines. Poly A mRNA was electrophoresed, immobilized on a nylon membrane and hybridized using α 32 P‐CTP labelled human ACTH‐R and P450scc cDNAs. RESULTSMean ACTH‐R mRNA expression showed significant differences between groups ( P =0.0001), but appeared to be independent of plasma ACTH concentrations. Compared to normal adrenal =100±12%), expression was low in non‐functional adenomas (23±11%) and carcinomas (19±12%), intermediate in adrenocortical hyperplasias (88±6%) and cortisol‐producing adenomas (81±15%) and high in aldosteronomas (175±29%). In adenomas, ACTH‐R mRNA expression correlated closely with the expression of P450scc mRNA r =0.8, P =0.0001) suggesting regulation by similar factors. However, carcinomas and cancer cell lines did not show a positive correlation between these two parameters r =−0.44, P =0.2). CONCLUSIONSWe have demonstrated that plasma ACTH is not the major factor influencing ACTH‐receptor mRNA expression in neoplastic adrenal tissue. In benign tumours of the adrenal cortex there was a close positive correlation between ACTH‐receptor mRNA and P450scc mRNA which was missing in adrenocortical carcinomas, probably as a result of tumour dedifferentiation.