Endocrine Abstracts

Somatostatin acts as an inhibitor of hormonal secretion and cell proliferation by acting through 5 somatostatin receptors subtypes (sst1–5). Coupling with Gi/o proteins is associated with effects on various transduction pathways, as adenylate cyclase inhibition or phosphatases activation. Dopamine receptor subtype 2 (D2DR) acts through coupling with similar G-proteins and transduction pathways. Sst, mostly sst2 and sst5, are coexpressed with D2DR in many neuroendocrine no...

Somatotroph pituitary adenomas are characterized by unrestrained hormone secretion and cell proliferation alterations. In those tumors, the only mutation so far unequivocally identified is the gsp oncogene (Gsα protein gain of function mutation). Nethertheless, there is no clear difference in the clinical phenotypes of patients bearing tumor with the gsp oncogene (gsp+) or not (gsp−). In addition, an overexpression of the wild-type Gsα protein has been o...

Somatic mutations of the αs subunit of G proteins were initially reported by Landis and collaborators in 1989 in somatotroph tumors characterized by markedly high cAMP levels. These mutations are localized at two critical sites concerning the intrinsic guanosine triphosphatase activity of the protein leading to a constitutive activation of the adenylyl cyclase. The mutated protein has been named the gsp oncogene. On the other hand, Gsα mRNA level varied among ...

Introduction: Pancreatic neuroendocrine neoplasms (PNEN) present with a fibrotic stroma which constitutes the tumor microenvironment (TME). The role played by stromal fibroblasts over the growth of PNEN and their sensitivity to the mTOR inhibitor, RAD001, are as yet unestablished.Methods: We investigated reciprocal interactions between 1) human PNEN cell lines (BON-1/QGP-1) or primary cultures of human ileal neuroendocrine neoplasm (iNEN) or PNEN, and 2)...

Background: Multiple endocrine neoplasia type 2 associated medullary thyroid carcinoma (MTC) is driven by a strong genotype-phenotype correlation, the risk of aggressiveness being defined by the germline RET pathogenic variant (American Thyroid Association (ATA) guidelines). Based on this classification, the germline c.2370G>C, p.Leu790Phe (L790F) RET variant is considered to be of moderate risk of aggressive MTC, while the germline c.2753T>C, p.Met918Thr (M9...

Context: Postzygotic activating mutations in GNAS are responsive for fibrous dysplasia (FD) and McCune-Albright Syndrome (MAS). MAS is a rare disease associating fibrous dysplasia, to skin pigmentation and endocrine disorders. The classic genetic non-invasive methods are insufficiently sensitive to detect GNAS mutation, due to a low level of mosaicism in blood. Early diagnostic should allow a follow-up and a therapeutic choice adapted to the MAS context in or...

The Ras/Raf/MEK/ERK is a conserved signalling pathway involved in the control of fundamental cellular processes. Despite extensive research, how this pathway can process a myriad of diverse extracellular inputs into specific biological outcomes is not fully understood. Particularly, the role of this pathway in neuroendocrine tumoral cells remains unclear.We have previously shown that the ERK1/2 pathway is an integrative point in the control of the pituit...

Somatostatin is a ubiquitous neuropeptidic inhibitor of various cellular functions including endocrine and exocrine secretion. Moreover, this peptide may control cell proliferation in normal and tumoral tissues. Somatostatin biological effects are mediated by five subtype of G protein-coupled receptor, sst1 through sst5. The somatostatin analogs have high affinity for sst2 receptor and the success of in vivo peptide therapy is correlated with high levels of sst2 in th...

Somatotroph adenomas are characterized by growth hormone hypersecretion and cell proliferation. We have previously identified crosstalk between the cAMP pathway and the MAPKinases ERK1/2 cascade and shown the central place of the MAPKinases in the control of the pituitary function in GH4C1 somatolactotroph cell line.The spatio-temporal organization of the signalling partners governs signalling fidelity and encodes the specificity of biological responses....

Pituitary tumors are most usual intracranial tumors, displaying hormonal hyper-secretion with in some cases a sustained cell proliferation. The somatotroph adenomas are characterised by a GH hypersecretion. The current treatments are based on somatostatinergic or dopaminergic agonists. Unfortunately, there is steel 50% of patients, which remain insensitive to these treatments. The aim of our work is to find a pharmacological alternative to treat the patients resistant to the c...