Elevation of growth hormone secretagogue receptor type 1a mRNA expression in human growth hormone-secreting pituitary adenoma harboring G protein alpha subunit mutation

Abstract

Objective: The purpose of this study was to investigate the relationship between the ghrelin or GHSR-1a mRNA levels and clinical characteristics and to confirm the effect of gsp mutations on ghrelin/GHSR-1a system in human GH-secreting pituitary adenomas.

Methods: The expression levels of ghrelin, GHSR-1a mRNA were determined by SYBR green real-time fluorescent quantitative PCR. The gsp mutations in 43 cases of human GH-secreting pituitary adenomas were detected using PCR-DNA direct sequencing analysis. Clinical data were obtained from the medical records of 43 acromegalic patients who had GH and IGF-1 assays in the same laboratory.

Results: The expression of GHSR-1a correlated positvely with tumor size (R=0.411, p=0.006) and invasiveness (p<0.05). In contrast, ghrelin mRNA levels correlated positively only with tumor size (R=0.331, p=0.030) but not with tumor invasiveness (p>0.05). The expression level of GHSR-1a mRNA was significantly higher in gsp positive adenomas than in negative adenomas (p<0.05). Whereas, there was no significant difference in the expression of ghrelin mRNA between gsp mutation-positive and -negative adenomas (p>0.05). Additionally there was a significant positve correlation between the ghrelin and GHSR-1a mRNA expression levels in gsp-positive (R=0.553, p=0.040) or -negative adenomas (R=0.489, p=0.007).

Conclusions: GHSR-1a correlated positively with tumor size and invasiveness, while ghrelin correlated positively only with tumor size. Gsp mutations may upregulate the expression of GHSR-1a mRNA and have no effect on ghrelin mRNA levels in human GH-secreting pituitary adenomas.