Details

Autor(en) / Beteiligte

• Regazzo, D
• Losa, M
• Albiger, N M
• Terreni, M R
• Vazza, G
• Ceccato, F
• Emanuelli, E
• Denaro, L
• Scaroni, C
• Occhi, G

Titel

The GIP/GIPR axis is functionally linked to GH-secretion increase in a significant proportion of gsp - somatotropinomas

Ist Teil von

• European journal of endocrinology, 2017-05, Vol.176 (5), p.543

Ort / Verlag

England

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Glucose-dependent insulinotropic polypeptide receptor ( ) overexpression has been recently described in a proportion of somatotropinomas and suggested to be associated with the paradoxical increase of GH (GH-PI) during an oral glucose load. 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 -expressing somatotropinomas, all of them negative for mutations, show increased GH secretion upon GIP stimulation, higher sensitivity to Forskolin but not to somatostatin analogs. Besides increased frequency of GH-PI, overexpression does not appear to affect acromegalic patients' clinical features. In STC-1 cells transfected with GIP promoter-driven luciferase vector, IGF-1 but not GH induced dose-dependent increase in luciferase activity. We demonstrate that mediates the GH-PI in a significant proportion of acromegalic patients. In these cases, the stimulatory effect of IGF-1 on GIP promoter support the hypothesis of a functional GH/IGF-1/GIP axis. Further studies based on larger cohorts and the development of a stable transgenic model with inducible GIPR overexpression targeted to pituitary somatotroph lineage will be mandatory to establish the real role of GIPR in the pathogenesis of somatotropinomas.