👤 G Vazza

Acromegaly, primarily caused by GH-secreting pituitary neuroendocrine tumors (GH-PitNETs), in about half of cases exhibits resistance to somatostatin receptor ligands (SRLs), making surgery the primary treatment. Recent evidence suggests that glucose-dependent insulinotropic polypeptide receptor (GIPR) overexpression in a subset of GH-PitNETs contributes to disease heterogeneity, particularly in tumors showing a paradoxical GH rise after glucose load, which are associated with a less aggressive phenotype and better first-generation SRLs response. This study investigated the functional role of GIPR in somatotroph cells by generating stable human GIPR-expressing GH3 cells (GH3hGIPR) and comparing them with empty vector controls. Functional assays demonstrated that GIPR activation induces cAMP/PKA and MAPK/ERK signaling, enhances GH and prolactin secretion, and increases intracellular calcium oscillations, dependent on extracellular calcium influx. Transcriptomic analysis revealed differential gene expression patterns linked to cell motility, neuronal development, and extracellular matrix remodeling in GH3hGIPR cells, aligning with clinical observations in GIPR+ tumors. However, GIPR overexpression did not alter cell proliferation or viability, suggesting that its role in tumor behavior may depend on additional molecular or epigenetic factors. These findings highlight the importance of GIPR signaling in somatotroph cell function and its potential influence on therapeutic responses, though further studies are needed to clarify its contribution to tumorigenesis and SRL sensitivity. Show less

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 Show less

Glucose-dependent insulinotropic polypeptide receptor ( This study was aimed at linking the GIP/GIPR pathway to GH secretion in 25 somatotropinomas-derived primary cultures and correlating molecular with clinical features in acromegalic patients. Given the impairment of the GIP/GIPR axis in acromegaly, an additional aim was to assess the effect of GH/IGF-1 stimulation on GIP expression in the enteroendocrine cell line STC-1. Nearly 80% of We demonstrate that Show less