Loss of growth hormone secretagogue receptor 1a and overexpression of type 1b receptor transcripts in human adrenocortical tumors.

Abstract

OBJECTIVE AND METHODS:

Quantitative analysis of mRNA expression of ghrelin and its receptors GHS-R1a and -R1b in a large series of normal and neoplastic human adrenocortical tissues. Evaluation of the effects of ghrelin on GHS-R expression and proliferation of human adrenocortical carcinoma (ACC) cell lines.

RESULTS:

Ghrelin and GHS-R transcripts are expressed in normal adrenal cortex, with GHS-R1b mRNA levels being 5- to 10-fold higher than GHS-R1amRNA. A significant increase in ghrelin expression was observed in adrenocortical adenomas, but not in carcinomas. GHS-R1a was undetectable in about 60% of both benign and malignant tumor samples, except for cortisol-producing adenomas, which showed increased receptor expression. At variance, GHS-R1b was overexpressed in both benign and malignant adrenocortical tumors. In vitro studies in human ACC cell lines demonstrated that GHS-R1a is downregulated and GHS-R1bmRNA expression is upregulated by ghrelin, while inhibiting cell proliferation.

CONCLUSION:

Downregulation ofGHS-R1a in adrenal tumors and the presence of high levels of GHS-R1b transcripts in adrenocortical tissue suggest a role for these receptors in adrenal function and growth. In this regard, ghrelin inhibits cell proliferation and modulates GHS-R expression in ACC cells in vitro.

• Authors: Luisa Barzon, Monia Pacenti, Giulia Masi, Anna-Lisa Stefani, Karina Fincati, Giorgio Palù
• Journal: Oncology (Oncology) Vol. 68 Issue 4-6 Pg. 414-21 ( 2005) ISSN: 0030-2414 [Print] Switzerland
• PMID: 16020971 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2005 S. Karger AG, Basel

Chemical References

• Ghrelin
• Peptide Hormones
• Peptides
• RNA, Messenger
• Receptors, G-Protein-Coupled
• Receptors, Ghrelin
• Growth Hormone

Topics

• Adrenal Cortex (metabolism)
• Adrenal Cortex Neoplasms (genetics, metabolism)
• Adrenocortical Adenoma (genetics, metabolism)
• Adrenocortical Carcinoma (genetics, metabolism)
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Ghrelin
• Growth Hormone (pharmacology)
• Humans
• Peptide Hormones (pharmacology)
• Peptides (genetics, metabolism)
• RNA, Messenger
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Receptors, Ghrelin
• Tumor Cells, Cultured