Glucose-dependent insulinotropic polypeptide (GIP) receptor is a member of the G protein-coupled receptors family. According to its incretin properties, GIPR is expressed in tissues such as pancreas, stomach and adipose tissue. However GIPR expression pattern appears to be broader, as it was detected in other tissues such as heart, lung and the central nervous system, thus suggesting either novel ligands for GIPR or novel actions for GIP. Moreover, in some patients with food-dependent Cushings syndrome, ectopical expression of GIPR was demonstrated being sufficient for inducing symptoms of hypercortisolemia and the formation of a benign adrenocortical tumor.
For such reasons, and in order to establish its possible involvement in pituitary adenomas tumorigenesis, GIPR expression was investigated in a large cohort of pituitary adenomas.
The study population consisted of 42 pituitary adenomas obtained after transsphenoidal surgery and 12 normal pituitary glands with autoptic origin (NPG). Based on the hormonal pattern and immunohistochemical studies 9 adenomas were classified as corticotropinomas, 12 were somatotropinomas (GHomas), 6 prolactinomas and 15 non-functioning pituitary adenomas (NFPAs).
Expression studies demonstrated that 5/12 GHomas and a single NFPA showed high GIPR expression compared to NPG in which low levels were detected. Similarly, low levels were observed in all other samples. The evaluation of clinical and biochemical parameters of acromegalic patients, revealed that for the only three high-GIPR expressing subjects, for which the OGTT was available, a paradoxical increase of GH after oral glucose load was observed. Such an effect was never observed in low-GIPR expressing subjects.
This data together lead us to hypothesize that in GHomas, GIPR may be possibly involved in the mechanism of GH-regulation exerted by the glucose, whereas it probably does not play any role in the pathogenesis of the other pituitary adenomas. Further studies are mandatory to establish the real role of GIPR in acromegaly.
03 - 07 May 2008
European Society of Endocrinology