Endocrine Abstracts

Neurosurgery is the treatment of choice of non-functioning pituitary tumors (NFPAs), but its success is strongly affected by local invasion. Medical therapy is still under debate, although the use of cabergoline results in tumor shrinkage in a subset of patients. We recently demonstrated that dopamine receptor DRD2 agonist BIM53097 exerts cytostatic and cytotoxic effects in cultured cells from NFPAs, but no data are present in literature about DRD2 mediated effects on pituitar...

Non-functioning pituitary tumors (NFPTs), although benign in nature, frequently present local invasiveness that strongly reduces neurosurgery success. Medical therapy is still under debate, although dopamine (DA) receptor 2 (DRD2) agonists may induce tumor shrinkage in some patients. Aims of this study were: 1) to evaluate the effect of DR2D agonist BIM53097 on migration and invasion of NFPT cells, 2) to investigate the molecular mechanisms regulating the motility of these cel...

Several studies support the existence of multipotent stem/progenitor cells in the adult pituitary, whereas the presence of stem cell in pituitary tumors and their role in pituitary tumorigenesis are still on debate. Aim of this study was to identify and characterize stem-like cells in non-functioning pituitary adenomas (NFPAs). To this purpose primary cell cultures from 25 NFPAs were grown in culture conditions that favored stem cell growth (EGF, bFGF and B27 containing medium...

The actin binding protein filamin A (FLNA) is required for somatostatin receptor 2 (SST2) and dopamine receptor 2 (DRD2) expression, intracellular localization and signaling in GH- and PRL-secreting pituitary tumors, respectively, playing a role in tumor responsiveness to somatostatin analogs and dopaminergic drugs. FLNA functions are tightly regulated by several mechanisms, including FLNA phosphorylation. It has recently been shown that in GH-secreting pituitary tumors FLNA p...

cAMP is implicated in the inhibition or stimulation of proliferation depending on cell type. The activation of cAMP–PKA pathway generates proliferative signals in GH-secreting adenomas whereas this effect is not present, or even opposite, in non-functioning pituitary cells (NFPA). Although cAMP effects were initially attributed to PKA activation, recently the discovery of two cAMP-activated guanine nucleotide exchange factors (Epac1,2) was proposed as a novel mechanism fo...

Despite the increasing evidence on the relevance of the actin binding protein filamin A (FLNA) in determining an efficient intracellular response to somatostatin analogs (SSA) in pituitary tumors, there is a gap in the knowledge on the mechanisms regulating FLNA itself. FLNA is phosphorylated by PKA on Ser2152 located in a FLNA region crucial for SST2 or partner proteins binding. Although cAMP/PKA pathway plays a crucial role in GH-secreting tumors pathogenesis, the...

Currently, the multi-ligand somatostatin (SS) analogue pasireotide (SOM230) is the only pituitary-targeted drug used to treat patients with Cushing’s disease. SOM230 displays the highest affinity to somatostatin receptor type 5 (SSTR5) and compared to octreotide resulted more effective in reducing ACTH release. Despite its anti-secretory role, SOM230 has been associated with tumor shrinkage in patients subjected to long term treatment, although to date the key factors inv...

Adrenocortical carcinomas (ACCs) are rare endocrine tumors with poor prognosis. The insulin-like growth factor 2 (IGF2) is overexpressed in the great majority of ACC, and IGF2/IGF1R pathway acts as a proliferative autocrine loop, but to date IGF1R-targeted therapies have demonstrated a limited efficacy and the molecular mechanisms regulating this pathway are still unknown. The cytoskeleton acting-binding protein filamin A (FLNA), determinant in cancer progression and metastasi...

Cushing’s Disease (CD) is a rare condition characterized by an overproduction of ACTH by an ACTH-secreting pituitary tumor, resulting in excess of cortisol release by the adrenal glands. Pasireotide is the pituitary-targeted drug approved to treat adult patients. Its mechanism of action seems to rely on the preferential binding to the highly expressed somatostatin receptor in corticotroph tumors, SST5. Recently, somatic mutations in the deubiquitinase USP8 gene h...

The high expression of somatostatin receptor 2 (SST2) in growth hormone (GH)-secreting tumors represents the rationale for the clinical use of somatostatin analogs (SSAs) in acromegaly. However, about one third of patients displays resistance to SSAs and, to date, the responsible molecular mechanisms are still under investigation. Recently, the cytoskeletal protein Filamin A (FLNA) and the scaffolding proteins β-arrestins have emerged as key modulators of the responsivene...