摘要：

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 32P-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.

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