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

M Reincke1, F Beuschlein, A C Latronico

  • 1Department of Internal Medicine, University of Würzburg, FRG.

Clinical Endocrinology
|May 1, 1997
PubMed
Abstract

Insights

Adrenocorticotrophin receptor (ACTH-R) mRNA expression differs in adrenal tumors. In benign tumors, ACTH-R mRNA correlates with P450scc mRNA, but this correlation is lost in carcinomas, suggesting dedifferentiation.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Adrenocorticotrophin (ACTH) regulates steroid secretion via the ACTH receptor (ACTH-R).
  • Cloning of the ACTH-R enables study of its role in adrenal tumorigenesis.
  • Investigating ACTH-R and P450 side-chain cleavage enzyme (P450scc) mRNA expression is crucial for understanding adrenal neoplasms.

Purpose of the Study:

  • To investigate ACTH-R and P450scc mRNA expression in various neoplastic adrenocortical tissues.
  • To determine the relationship between ACTH-R mRNA expression and plasma ACTH concentrations.
  • To explore the correlation between ACTH-R and P450scc mRNA in normal and neoplastic adrenal tissues.

Main Methods:

  • Analysis of mRNA expression using Northern blot and reverse-transcriptase-PCR (RT-PCR).
  • Studied tissues included normal adrenals, hyperplasias, adenomas, carcinomas, and cell lines.
  • Hybridization with radiolabeled human ACTH-R and P450scc cDNAs.

Main Results:

  • Significant differences in ACTH-R mRNA expression were observed across tissue groups (P=0.0001).
  • ACTH-R mRNA expression was low in non-functional adenomas and carcinomas, intermediate in hyperplasias and cortisol-producing adenomas, and high in aldosteronomas.
  • A strong positive correlation between ACTH-R and P450scc mRNA was found in adenomas (r=0.8, P=0.0001) but not in carcinomas (r=-0.44, P=0.3).

Conclusions:

  • Plasma ACTH levels do not significantly influence ACTH-receptor mRNA expression in neoplastic adrenal tissue.
  • A positive correlation between ACTH-receptor mRNA and P450scc mRNA exists in benign adrenal tumors.
  • The loss of this correlation in adrenocortical carcinomas likely indicates tumor dedifferentiation.

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