The GIP/GIPR axis is functionally linked to GH-secretion increase in a significant proportion of gsp- somatotropinomas.
Eur J Endocrinol
; 176(5): 543-553, 2017 May.
Article
in En
| MEDLINE
| ID: mdl-28179449
ABSTRACT
OBJECTIVE:
Glucose-dependent insulinotropic polypeptide receptor (GIPR) overexpression has been recently described in a proportion of gsp- somatotropinomas and suggested to be associated with the paradoxical increase of GH (GH-PI) during an oral glucose load. DESIGN ANDMETHODS:
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.RESULTS:
Nearly 80% of GIPR-expressing somatotropinomas, all of them negative for gsp mutations, show increased GH secretion upon GIP stimulation, higher sensitivity to Forskolin but not to somatostatin analogs. Besides increased frequency of GH-PI, GIPR 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.CONCLUSIONS:
We demonstrate that GIPR mediates the GH-PI in a significant proportion of gsp- 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pituitary Neoplasms
/
Receptors, Gastrointestinal Hormone
/
Gastric Inhibitory Polypeptide
/
Human Growth Hormone
/
Growth Hormone-Secreting Pituitary Adenoma
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Eur J Endocrinol
Journal subject:
ENDOCRINOLOGIA
Year:
2017
Document type:
Article
Affiliation country:
Italy