Correlation of ghrelin and growth hormone secretagogue receptor expression with clinical features in human pituitary adenomas.

Abstract

Ghrelin, as a brain-gut peptide, has growth hormone (GH)-releasing and appetite-inducing activities and a widespread tissue distribution. Furthermore, ghrelin is an endogenous ligand of the GH secretagogue receptor (GHSR), and both ghrelin and GHSR are expressed in the pituitary; however, the data regarding the expression of ghrelin and GHSR in pituitary adenomas are divergent and conflicting. In the present study, therefore, the expression of ghrelin and GHSR was examined in the full spectrum of human pituitary adenoma subtypes (n=34) and in normal pituitary tissue (n=3). The mRNA and protein expression levels were quantified using a competitive reverse transcription-polymerase chain reaction and western blotting and the correlation of the results with the clinical parameters was assessed. mRNA and protein expression of ghrelin and GHSR was detected in all samples with the highest mean level in GH adenomas, a moderate level in clinically non-functioning adenomas and the lowest level in adrenocorticotropin adenomas. A significant correlation between the ghrelin and GHSR mRNA expression levels was observed in the GH adenomas (n=12) (r=0.8435, P=0.0006). The ghrelin mRNA expression level in the GH adenomas correlated positively with the basic serum GH level (n=12) (r=0.6488, P=0.0225). Furthermore, the mean level of ghrelin mRNA expression was significantly higher in invasive adenomas than in noninvasive adenomas (P<0.01). Collectively, the results of the study provided evidence that ghrelin and GHSR are expressed in the various subtypes of pituitary adenoma, with specific overexpression in GH adenomas. The study suggests that the binding of ghrelin to GHSR promotes the secretion of GH and plays an important role in the development of GH adenomas via autocrine and/or paracrine effects.