Notch signaling pathway is involved in a wide group of processes including tumorigenesis and stem cell self-renovation. Nevertheless, its role in pituitary tumor generation has not been systematically addressed. Our principal goal was to evaluate if the pharmacological inhibition of Notch pathways alters somatolactotropic tumor growth, hormone secretion, and suppressor gene expression.700000 GH3 cells (somatolactotropic) were injected subcutaneously in the flank of Nude/Nude mice; after 21 days of growth the tumors were treated ip with DAPT, a gamma secretase inhibitor which interferes with Notch activation (8 mg/kg of body weight). After three weeks of treatment the tumors were extracted, measured and frozen for protein and gene expression. We used the information of existing ChIP-seq data to infer putative Notch1 regulatory regions in pituitary GC cells. These were defined as active enhancers (H3K4me1+/H3K27ac+/Pit1+) which we intersected with Notch1 binding (lifted over from T-ALL). Furthermore, we downloaded and reanalyzed public RNA-seq datasets from human Normal Pituitary and Pituitary Tumour samples and performed GSEA analysis to look for Notch signaling components altered in human pituitary adenomas. These in silico transcriptomic and epigenetic analyses allowed us to choose several tumor suppressors or enhancers of Notch signaling to be evaluated in our experiment: Btg2, Nur4A1, Delta like 1N, Men-1, Zfp35, and Cnot1Tumor volumes in animals treated with DAPT were in average 42% smaller than in the control group (tumoral mass + SE: 490 + 80,7 and 284+ 67,5 mm2, control and DAPT, n=12 y n=11 respectively, p