Expression of ghrelin and ghrelin functional receptor GHSR1a in human pituitary adenomas

INTRODUCTION    Pituitary adenomas are heterogenous lesions commonly observed in the central nervous system. Signal transduction of ghrelin, an endogenous ligand specific for growth hormone secretagogue receptor (GHSR), has been reported to be involved in the development of endocrine tumors. However, there are limited data concerning the role of ghrelin and its functional receptor in pituitary adenomas. OBJECTIVES    The aim of the study was to establish the expression pattern of GHRL and its functional receptor GHSR1a in human pituitary adenomas. PATIENTS AND METHODS    Tissue specimens, including somatotropinomas (n = 20), prolactinomas (n = 5), and nonfunctioning adenomas (n = 52) were obtained from 77 patients. Thirteen normal pituitaries served as controls. The expression pattern of GHRL and GHSR1a mRNAs was established using reverse transcription followed by quantitative polymerase chain reaction. RESULTS    Ghrelin mRNA was detected in 92.2% of the samples including controls, while GHSR1a transcripts were detected in 54.4% of the cases. Significant differences were found among subgroups in the GHSR1a expression (P <0.0001) but not in that of GHRL (P = 0.7). The relative GHSR1a expression level was significantly lower for nonfunctioning tumors than for the control group or somatotropinomas. Controls revealed a strong positive correlation between the expression of both genes (r = 0.8; P <0.0001), unlike adenomas, which showed a weak negative correlation (r = -0.3; P >0.05). The maximum tumor diameter for nonfunctioning adenomas was higher than that for somatotropinomas (mean [SD], 31.4 [76] mm vs 24.8 [10.9] mm; P = 0.01). Neither the GHRL nor GHSR1a expression showed a significant correlation with tumor size in the subgroups. CONCLUSIONS    The presence of GHRL and GHSR1a in the neural system indicates their effect on pituitary function regulation and suggests their possible role in adenoma pathogenesis.