Endocrine Abstracts

The novel somatostatin receptor agonist SOM230 (pasireotide) binds with high affinity to somatostatin receptors sst1, sst2, sst3 and sst5. Acting principally through the latter, it inhibits basal and CRH-stimulated ACTH secretion from the AtT20 mouse corticotroph cell line and ACTH release from a proportion of human corticotroph adenomas both in vitro and in vivo. Data suggesting an additional antiproliferative effect has led to SOM230 being explored as a potenti...

Somatostatin (somatotrophin release inhibiting factor; SRIF) is produced primarily in the hypothalamus and pancreas and inhibits the secretion of many hormones and neurotransmitters. Moreover, SRIF and SRIF analogs are able to inhibit tumor growth. Many human neuroendocrine and non-neuroendocrine tumors express the five known somatostatin receptors (sst1–5) in different amounts.Tachyphylaxis after prolonged treatment with octreotide (Sand...

Improved therapies for pancreatic and pituitary neuroendocrine tumors (NETs), which may occur in Multiple Endocrine Neoplasia type 1 (MEN1), are needed. We assessed the effects of pasireotide, a somatostatin analogue with high affinity for somatostatin receptors (SSTRs) −1, −2, −3 and −5, in a mouse model of MEN1. Men1+/− mice treated from 12 months of age with 40 μg/g pasireotide (n=71), or phosphate-buffered sal...

Background: AMPK is a metabolic enzyme regulating the energy supply of the cell but it has antiproliferative effects as well via the up-regulation of the p53-p21 axis and inhibition of the mTOR-pathway. Somatostatin (SST) analogues reduce hormone secretion from somatotroph adenomas and tumour growth inhibition can also be achieved. SST affect several signalling pathways including the mTOR-pathway. mTOR is a mediator of a pro-proliferative pathway that can be inhibited by activ...

Background: The PAOLA study assessed the efficacy/safety of pasireotide LAR vs continued treatment with octreotide LAR/lanreotide Autogel in patients with inadequately controlled acromegaly. An exploratory objective was to measure changes in various associated biomarkers, including IGF1 and IGFBP2 (released from white fat cells and known to prevent insulin resistance), glucose and HbA1c.Methods: Adult patients (GH >2.5 μg/l and IGF1 >1.3&#21...

Somatostatin (SRIF) analogs have been employed in medical therapy of non-functioning pituitary adenomas (NFA), with contrasting results. Previous evidence showed that SRIF can exert its antiproliferative effects by reducing Vascular Endothelial Growth Factor (VEGF) secretion and action, and that VEGF expression may be related to pituitary tumor growth. The aim of our study was to clarify the possible effects of a multireceptor SRIF ligand on VEGF secretion and cell proliferati...

Somatostatin analogs (SSA) are a first-line treatment for pituitary adenomas (PA). Indeed, multi-receptor targeting SSA such as octreotide and pasireotide are being successfully used to control hormone secretion and/or tumor growth. Unfortunately, many PA escape from SSA-therapy, which could be related to somatostatin receptor (sst) presence, abundance, availability and/or signaling. In order to better define the molecular/cellular features associated to octreotide and pasireo...