Searchable abstracts of presentations at key conferences in endocrinology

ea0032s11.2 | New mechanisms in SST analogue response | ECE2013

Role of filamin A in dopamine and somatostatin receptor targeting in the pituitary

Peverelli Erika

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...

ea0035p830 | Pituitary Basic (<emphasis role="italic">Generously supported by IPSEN</emphasis>) | ECE2014

Dopamine receptor type 2 (dopamine receptor type 2) inhibits non-functioning human pituitary tumor-derived cell line HP75 migration through ROCK-mediated cofilin inactivation

Treppiedi Donatella , Peverelli Erika , Giardino Elena , Spada Anna , Mantovani Giovanna

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...

ea0041ep853 | Pituitary - Basic | ECE2016

Human non-functioning pituitary tumors invasiveness: inhibitory effects of dopamine receptor type 2 (DRD2) agonist and cofilin involvement

Peverelli Erika , Giardino Elena , Treppiedi Donatella , Locatelli Marco , Vaira Valentina , Ferrero Stefano , Spada Anna , Mantovani Giovanna

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...

ea0037ep1121 | Endocrine tumours | ECE2015

Identification of human SST2 somatostatin receptor domains involved in receptor internalization and signaling in pancreatic neuroendocrine tumors

Cambiaghi Valeria , Vitali Eleonora , Mantovani Giovanna , Spada Anna , Peverelli Erika , Lania Andrea

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...

ea0035oc12.4 | Pituitary Basic | ECE2014

Identification and characterization of pituitary adenoma stem-like cells in human non functioning pituitary adenomas

Giardino Elena , Peverelli Erika , Treppiedi Donatella , Belicchi Marzia , Meregalli Mirella , Spada Anna , Torrente Yvan , Mantovani Giovanna

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...

ea0070aep584 | Pituitary and Neuroendocrinology | ECE2020

A novel mechanism regulating dopamine receptor type 2 (DRD2) signal transduction in PRL- and ACTH-secreting pituitary tumoral cells: The role of cAMP/PKA-induced filamin A (FLNA) phosphorylation in the control of responsiveness to DRD2 agonist

Mangili Federica , Treppiedi Donatella , Catalano Rosa , Giardino Elena , Arosio Maura , Spada Anna , Mantovani Giovanna , Peverelli Erika

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...

ea0032p827 | Pituitary–Basic (<emphasis role="italic">Generously supported by IPSEN</emphasis>) | ECE2013

cAMP exerts proliferative and anti-proliferative effects in pituitary cells of different types by activating both cAMP-dependent protein kinase A and exchange proteins directly activated by cAMP

Vitali Eleonora , Peverelli Erika , Mantovani Giovanna , Giardino Elena , Lania Andrea G. , Beck-Peccoz Paolo , Spada Anna

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...

ea0022p720 | Signal transduction | ECE2010

Role of filamin-A in the regulation of dopamine D2 receptor localization and signaling in a lactotroph cell model

Mantovani Giovanna , Peverelli Erika , Ferrero Stefano , Vitali Eleonora , Beck-Peccoz Paolo , Spada Anna , Lania Andrea

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...

ea0020p585 | Neuroendocrinology, Pituitary and Behaviour | ECE2009

Genetic alterations of phosphodiesterase 11A (PDE11A) in acromegalic patients

Peverelli Erika , Ermetici Federica , Filopanti Marcello , Lania Andrea , Ferrero Stefano , Beck-Peccoz Paolo , Spada Anna

Background: Aberrant cAMP signalling is involved in the pathogenesis of somatotropinomas. Recently, variants of phosphodiesterase type 11A (PDE11A) gene have been described in patients with adrenocortical tumors. Aim of the study was to investigate the presence of these variants in patients with somatotropinomas.Subjects and methods: Germ-line DNA of 78 acromegalic patients was screened for known genetic variants of PDE11A by direct sequencing or restric...

ea0016p658 | Signal transduction | ECE2008

G protein coupling and adenylyl cyclase inhibition are mediated by the DRY motif in the second intracellular domain of the SST5 receptor

Peverelli Erika , Lania Andrea , Mantovani Giovanna , Bondioni Sara , Beck-Peccoz Paolo , Spada Anna

Somatostatin exerts inhibitory effects on hormone secretion and cell proliferation by interacting with five different receptors (SST1–SST5) linked to effector systems via G proteins. The receptor structural domains mediating these effects have not been identified. Since SS is the hypothalamic peptide that physiologically inhibits GH secretion, aim of this study was to investigate the molecular determinants mediating the interaction of the human SST5 with G proteins and su...