Endocrine Abstracts

Prolactinomas are the most frequent pituitary tumors, and dopamine agonists (DA) are their first-choice treatment, since they normalize PRL levels and reduce tumor size in the majority of patients, by binding to dopamine receptor type 2 (DRD2) on tumoral cells. However, drug resistance occurs in a subset of patients, involving different steps following receptor activation or during the final biological responses. Although resistance to DA has been correlated with a reduced DRD...

Molecular mechanisms underlying resistance of pituitary tumors to somatostatin (SS) and dopamine (DA) analogs treatment are not completely understood. Resistance has been associated with defective expression of functional SS (SSTR2–5) and DA (DRD2) receptors. The role of cytoskeleton proteins in receptor trafficking, anchoring to the plasma membrane and signalling has been demonstrated in other tumoral cell systems. In particular, filamin A (FLNA) seems to be a good candi...

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...

Somatostatin exerts its inhibitory effects on hormone secretion and cell proliferation via five receptors subtypes (SST1-SST5). After agonist binding, receptor residues mainly located in the carboxyl terminal (CT) and in the third intracellular loop (IC3) are phosphorylated and β-arrestins are recruited to drive SSTRs internalization.Aim of the study is to characterize the intracellular mechanisms responsible for SST2 internalization and identify th...

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...

In this study we employed a novel bioluminescence resonance energy transfer (BRET) biosensor to study the coupling specificity of somatostatin receptor 5 (SST5) and its naturally occurring mutant R240W in living cells. Our previous data demonstrated that SST5 carrying the R240W mutation as well as other mutations in the third intracellular loop maintained the ability to inhibit intracellular cAMP levels similarly to the wild-type but failed to mediate the inhibition of intrace...

Dopamine agonists (DA) inhibit prolactin (PRL) secretion and expression on the pituitary lactotrophs by binding dopamine D2 receptor. Prolactinomas are the most common secreting pituitary adenomas, and DA are the first choice for their treatment because they reduce PRL levels and tumor size. However, a subset of patients is resistant to DA. The mechanisms involved in DA resistance are not fully understood, although decreased expression of D2 receptor or altered signal transduc...