Searchable abstracts of presentations at key conferences in endocrinology

ea0081oc7.1 | Oral Communications 7: Pituitary and Neuroendocrinology 2 | ECE2022

Splicing factor 3 subunit B1 (SF3B1) inhibition in PRL-secreting PitNETs and cross-talk with dopamine receptor type 2 (DRD2)

Di Muro Genesio , Mangili Federica , Barbieri Anna Maria , Esposito Emanuela , Treppiedi Donatella , Arlati Federico , Catalano Rosa , Marra Giusy , Nozza Emma , Arosio Maura , Mantovani Giovanna , Peverelli Erika

Somatic mutations in splicing factor 3 subunit B1 (SF3B1) were found in about 20% of PRL-secreting PitNETs. SF3B1 is involved in pre-mRNA splicing and required for assembly of the U2 complex, which is critical for branch site recognition and the early stages of spliceosome assembly. Patients with mutant prolactinomas showed higher PRL levels and shorter progression-free survival compared to wild-type patients. Aims of the present study were: 1) to characterize the genetic prof...

ea0081p179 | Pituitary and Neuroendocrinology | ECE2022

Role of beta arrestins and G proteins in mediating DRD2 signaling in pituitary tumors

Esposito Emanuela , Mangili Federica , Di Muro Genesio , Maria Barbieri Anna , Treppiedi Donatella , arlati federico , Catalano Rosa , Marra Giusy , nozza emma , Arosio Maura , Mantovani Giovanna , Peverelli Erika

Dopamine receptor type 2 (DRD2) agonists (DA) are the first-choice treatment for prolactin (PRL)-secreting pituitary tumors, but poorly effective in non-functioning (NF)-PitNETs. Along with G protein-dependent signaling, DRD2 also mediates non-canonical beta-arrestin-dependent pathways, where reduction of AKT phosphorylation plays a leading role for the antiproliferative effect of DRD2 in pituitary tumors. Through UNC9994 and MLS1547, a beta-arrestin 2-biased and a G protein-b...

ea0081ep49 | Adrenal and Cardiovascular Endocrinology | ECE2022

The different contribution of IGF1R and IR in mediating insulin-like growth factor 2 (IGF2) effects in adrenocortical carcinomas

Catalano Rosa , Nozza Emma , Esposito Emanuela , Barbieri Anna Maria , Marra Giusy , Treppiedi Donatella , Mangili Federica , Di Muro Genesio , Arlati Federico , Morelli Valentina , Arosio Maura , Mantovani Giovanna , Peverelli Erika

Adrenocortical carcinomas (ACCs) are rare endocrine tumors with poor prognosis. They overexpress the insulin-like growth factor 2 (IGF2), that drives a proliferative autocrine loop by binding to IGF1R and IR. The majority of studies focused on IGF1R as mediator of IGF2 biological effects, but recently a high expression of IR, in particular of the isoform A, was observed in most ACCs, suggesting a potential role of this receptor in modulating IGF2 effects in adrenocortical tumo...

ea0073oc8.4 | Oral Communications 8: Pituitary and Neuroendocrinology | ECE2021

Novel insight into ACTH-secreting pituitary tumors biological behavior: hormone secretion and cell proliferation modulation by Ubiquitin Specific Peptidase 8 inhibitor RA-9

Di Muro Genesio , Treppiedi Donatella , Marra Giusy , Mangili Federica , Catalano Rosa , Barbieri Anna Maria , Locatelli Marco , Spada Anna , Arosio Maura , Mantovani Giovanna , Peverelli Erika

Cushing’s Disease (CD) is a rare condition mostly caused by an ACTH-secreting pituitary tumor resulting in excess of cortisol release by the adrenal glands. Although pasireotide is the only pituitary-targeted drug approved to treat adult patients, many side effects are encountered during the clinical practice and a curative therapy for CD is still challenging. Recently, the discover of somatic mutations in the deubiquitinase USP8 gene in a subset of patients has ...

ea0081p168 | Pituitary and Neuroendocrinology | ECE2022

Impact of USP8 mutations on corticotroph tumor cells responsiveness to pasireotide

Peverelli Erika , Marra Giusy , Treppiedi Donatella , Di Muro Genesio , Esposito Emanuela , Maria Barbieri Anna , Catalano Rosa , Mangili Federica , Locatelli Marco , Lania Andrea , Ferrante Emanuele , Indirli Rita , Spada Anna , Arosio Maura , Mantovani Giovanna

Somatic mutations in the ubiquitin specific peptidase 8 (USP8) gene have been associated with higher levels of somatostatin (SS) receptor subtype 5 (SSTR5) in adrenocorticotroph hormone (ACTH)-secreting pituitary neuroendocrine tumors (PitNETs). However, a correlation between the USP8 mutational status and favorable responses to pasireotide, the somatostatin multi-receptor ligand acting especially on SSTR5, has not been investigated yet. Here, we studied the impact of USP8 mut...

ea0081p174 | Pituitary and Neuroendocrinology | ECE2022

The positive feedback exerted by mtor inhibitor everolimus in pituitary neuroendocrine tumoral cells is reverted by cabergoline co-treatment

Mangili Federica , Esposito Emanuela , Treppiedi Donatella , Catalano Rosa , Marra Giusy , Di Muro Genesio , Maria Barbieri Anna , Locatelli Marco , Gerardo Lania Andrea , Spada Anna , Arosio Maura , Mantovani Giovanna , Peverelli Erika

The mTOR inhibitor everolimus has been shown to display antimitotic effects on diverse neoplasms, including pituitary neuroendocrine tumors (PitNETs); however, its effect is reduced by an escape mechanism that increases AKT phosphorylation (P-AKT) leading to survival pathway activation. Dopamine receptor type 2 (DRD2) reduces p-AKT in some non-functioning PitNETs (NF-PitNETs) and in lactotrophs MMQ cells, through a α-arrestin 2-dependent mechanism. This study aim...