Differential expression of ghrelin and its receptor (GHS-R1a) in various adrenal tumors and normal adrenal gland

Abstract

Ghrelin is a newly characterized, widely distributed peptide thought to be involved in the regulation of appetite. Significant effects on the release of growth hormone (GH) and ACTH have been demonstrated. This study compares the expression of ghrelin and its receptor (GHS-R) in various adrenal tumors and normal adrenal gland. Normal adrenal tissue was obtained after autopsy. Tissue was obtained from 13 pheochromocytomas (PHEOs), 15 cortisol-secreting adenomas (CPAs), 12 aldosterone-secreting adenomas (APAs), and 16 nonfunctional adenomas (NFAs) following laparoscopic surgery. Expression of ghrelin and GHS-R1a was investigated on RNA levels by using real-time reverse transcription polymerase chain reaction (RT-PCR) and on protein levels by using immunohistochemistry. In the seven normal adrenal glands analyzed, ghrelin mRNA levels were 12-fold lower than in stomach. Ghrelin protein expression was confirmed by immunohistochemistry. In all adrenal tumors, relevant levels of ghrelin mRNA were observed, with significantly lower expression in PHEOs and APAs than in normal adrenal gland. Ghrelin protein was detected in 0% of PHEOs, 55% of APAs, 87% of CPAs, and 54% of NFAs. GHS-R1a mRNA expression was detectable in normal adrenal gland, but the receptor protein was absent. In adrenal tumors, detectable levels of receptor mRNA were found in 38% of PHEOs, 13% of CPAs, and 25% of NFAs. GHS-R1a protein was absent in the majority of adrenal tumors. Expression of ghrelin in normal adrenal gland and adrenal tumors may indicate some unknown physiological function. The pathophysiological relevance of ghrelin expression in adrenal tumors remains to be investigated.