Endocrine Abstracts

IGF1 represents an important growth factor in pituitary physiology and pathology, also mediating the negative feed-back mechanisms on somatotroph axis. It has been previously demonstrated that IGF1 promotes cell viability in primary cultures of human non functioning pituitary adenomas, by a mechanisms involving, at least in part, mTOR signaling, which is involved in many pathways controlling proliferation. We aimed at investigating whether mTOR may mediate IGF1 effects also in an in vitro model of GH/PRL secreting pituitary adenoma, the rat GH3 cells. Therefore, GH3 cells were incubated in the presence or in the absence of 100 nM IGF1 with either Everolimus, an mTOR inhibitor, or NVP-BEZ235, a PI3K/mTOR inhibitor at concentrations ranging from 10 to 500 nM for 72 h. We found that the lowest Everolimus concentration that significantly inhibits cell viability is 25 nM, with a cell viability reduction of 50% (P<0.01). The lowest NVP-BEZ235 concentration that significantly inhibits cell viability is 50 nM, with a cell viability reduction of 40% (P<0.01). In addition, IGF1 significantly (P<0.05) increased GH3 cell viability by 20–60% at concentrations ranging from 10 to 500 nM, independently of the concentration. These proliferative effects were completely abrogated by co-incubation with 50–100 nM Everolimus or NVP-BEZ235. On the other hand, 50–100 nM Everolimus or NVP-BEZ235 significantly promoted caspase 3/7 activity (15–25%; P<0.02. Basal apoptotic rate was not significantly influenced by IGF1, which did not protect GH3 cells from proapoptotic effects of Everolimus and of NVP-BEZ235. These results confirm that IGF1 has proliferative effects on pituitary adenoma cells, which are mediated, at least in part by mTOR. On the contrary, IGF1 does not prevent the pro-apoptotic effects of mTOR inhibitors.