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

M Reincke, F Beuschlein, A C Latronico, W Arlt, G P Chrousos, B Allolio

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)


OBJECTIVE: Adrenocorticotrophin (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 MEASUREMENTS: We 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 alpha 32P-CTP labelled human ACTH-R and P450scc cDNAs.

RESULTS: Mean 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 = 0.3).

CONCLUSIONS: We 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.

Original languageEnglish
Pages (from-to)619-26
Number of pages8
JournalClinical Endocrinology
Issue number5
Publication statusPublished - May 1997


  • Adenoma
  • Adrenal Cortex
  • Adrenal Cortex Neoplasms
  • Adult
  • Aged
  • Blotting, Northern
  • Carcinoma
  • Cholesterol Side-Chain Cleavage Enzyme
  • Humans
  • Hyperplasia
  • Middle Aged
  • Polymerase Chain Reaction
  • RNA, Messenger
  • Receptors, Corticotropin
  • Tumor Cells, Cultured


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