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


CONCLUSIONS
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.
Barzon
Luisa
L
Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy. luisa.barzon@unipd.it
Pacenti
Monia
M
Masi
Giulia
G
Stefani
Anna-Lisa
AL
Fincati
Karina
K
Palù
Giorgio
G
D000302:Adrenal Cortex / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism*; D018246:Adrenocortical Adenoma / Q000235:genetics / Q000378:metabolism*; D018268:Adrenocortical Carcinoma / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D054439:Ghrelin; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D036361:Peptide Hormones / Q000494:pharmacology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D054440:Receptors, Ghrelin; D014407:Tumor Cells, Cultured
D054439:Ghrelin; D036361:Peptide Hormones; D010455:Peptides; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013006:Growth Hormone