The Methylation Analysis of the <i>Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR)</i> Locus in GH-Secreting Pituitary Adenomas

Abstract

The glucose-dependent insulinotropic polypeptide receptor (GIPR) is aberrantly expressed in about one-third of GH-secreting pituitary adenomas (GH-PAs) and has been associated with a paradoxical increase of GH after a glucose load. The reason for such an overexpression has not yet been clarified. In this work, we aimed to evaluate whether locus-specific changes in DNA methylation patterns could contribute to this phenomenon. By cloning bisulfite-sequencing PCR, we compared the methylation pattern of the GIPR locus in GIPR-positive (GIPR+) and GIPR-negative (GIPR−) GH-PAs. Then, to assess the correlation between Gipr expression and locus methylation, we induced global DNA methylation changes by treating the lactosomatotroph GH3 cells with 5-aza-2′-deoxycytidine. Differences in methylation levels were observed between GIPR+ and GIPR− GH-PAs, both within the promoter (31.9% vs. 68.2%, p p Gipr steady-state level, possibly associated with the observed decrease in CpGs methylation. These results indicate that epigenetic regulation affects GIPR expression in GH-PAs, even though this possibly represents only a part of a much more complex regulatory mechanism.

Keywords

• glucose-dependent insulinotropic polypeptide receptor (GIPR)
• GH-secreting pituitary adenomas
• CpG methylation
• 5-aza-2′-deoxycytidine
• acromegaly