Searchable abstracts of presentations at key conferences in endocrinology

ea0070oc9.4 | Reproductive and Developmental Endocrinology | ECE2020

Demonstration of follicle-stimulating hormone receptor and G protein-coupled estrogen receptor heteromers in vitro via BRET and super-resolution imaging

Lazzaretti Clara , Sayers Niamh , Paradiso Elia , Sperduti Samantha , Fanelli Francesca , Simoni Manuela , Hanyaloglu Aylin , Casarini Livio

Introduction: The developmental stages of the ovarian follicle are characterized by changes of gonadotropin and steroid hormone receptor expression and their potential interactions on the surface of granulosa cells. In this study in vitro, we aim to evaluate whether the co-existing follicle-stimulating hormone receptor (FSHR) and G protein-coupled estrogen receptor (GPER) form heteromers, which may play role in selecting the dominant ovarian follicle.<p class="abs...

ea0070aep781 | Reproductive and Developmental Endocrinology | ECE2020

Luteinizing hormone/choriogonadotropin receptor (LHCGR) mediates different kinetics of G proteins, β-arrestins and cAMP activation

Paradiso Elia , Benevelli Riccardo , Lazzaretti Clara , Sperduti Samantha , Brigante Giulia , Simoni Manuela , Casarini Livio

Pituitary luteinizing hormone (LH) and placental human choriogonadotropin (hCG) are two heterodimeric glycoprotein hormones regulating reproduction. They bind the same receptor (LHCGR) expressed in gonadal cells, activating hormone-specific G protein- and β-arrestins-dependent signaling cascades, before LHCGR internalization. LH induces preferential proliferative signals, while hCG activates mainly the steroidogenic pathway, reflecting their physiological roles. In this s...

ea0081oc12.5 | Oral Communications 12: Reproductive and Developmental Endocrinology | ECE2022

Luteinizing hormone (LH)- and choriogonadotropin (hCG)-induced internalization of the receptor (LHCGR) is responsible for hormone-specific signaling

Paradiso Elia , Lazzaretti Clara , D'Alessandro Sara , Sperduti Samantha , Roy Neena , Mascolo Elisa , Baschieri Lara , Anzivino Claudia , Simoni Manuela , Casarini Livio

Introduction: Luteinizing hormone (LH) and human choriogonadotropin (hCG) regulate reproduction through binding the same receptor (LHCGR). They act via activation of G protein- and β-arrestin-dependent signals, resulting in ligand-specific pattern of signaling cascades and LHCGR internalization into endosomal vesicles. Previous studies differentiated the action of these two hormones in LH-related proliferative signals and hCG-related steroidogenic signals.Aim. We compared...

ea0081ep877 | Reproductive and Developmental Endocrinology | ECE2022

The endocrine disruptor Benzo[a]Pyrene inhibits gonadotropin-mediated steroidogenesis in a mouse Leydig tumor cell line

Sperduti Samantha , Roy Neena , Lazzaretti Clara , Paradiso Elia , D'Alessandro Sara , Mascolo Elisa , Baschieri Lara , Santi Daniele , Simoni Manuela , Casarini Livio

Introduction: Benzo[a]Pyrene (BaP) is an endocrine-disrupting chemical, which may impact reproduction. It is a polycyclic aromatic hydrocarbon generated by the incomplete combustion of organic compounds. BaP may be accumulated in the environment, achieving effective concentrations in the nanomolar range and exerting genotoxic effects in long-term exposed humans.Aim: We evaluated the short-term impact of BaP on luteinizing-hormone (LH)/choriogonadotropin ...

ea0090p468 | Reproductive and Developmental Endocrinology | ECE2023

In vitro evaluation of the impact of two differently glycosylated recombinant FSH on signal transduction

Mascolo Elisa , Baschieri Lara , Roy Neena , Lazzaretti Clara , Paradiso Elia , Perri Carmela , Sperduti Samantha , Simoni Manuela , Casarini Livio

Follicle stimulating hormone (FSH) is produced by the anterior pituitary gland and it is a key hormone in the reproductive system. FSH is a heterodimeric glycoprotein composed with two extensively glycosylated protein sobunits (α and β) N-glycosylated in two positions (Asn52 and Asn78 in the FSHα subunit and Asn7 and Asn24 in the FSHβ subunit) giving rise to numerous isoforms of FSH. Glycosylation has been shown t...

ea0063gp84 | Thyroid Nodules and Cancer | ECE2019

Polygenic susceptibility to papillary thyroid cancer: detection of the main genetic signature in Italian patients

Brigante Giulia , Lazzaretti Clara , Paradiso Elia , Foersti Asta , Hemminki Kari , Elisei Rossella , Romei Cristina , Simoni Manuela , Landi Stefano , Casarini Livio

Introduction and aim: Thyroid cancer is the most common endocrine neoplasia affecting 0.2–1.5% of the individuals worldwide and its incidence is increasing [1]. Papillary thyroid carcinoma (PTC) is the main histotype (80–90%). PTC susceptibility is the result of genetic predisposition, environmental factors and lifestyle. We hypothesized that genetic predisposition to PTC is poligenic and characterized by a genetic signature involving combinations of genes previously...

ea0070aep849 | Reproductive and Developmental Endocrinology | ECE2020

Aminoacidic residues discriminating human choriogonadotropin (hCG) and luteinizing hormone (LH) binding to the human receptor (LHCGR)

Lazzaretti Clara , Secco Valentina , Paradiso Elia , Sperduti Samantha , Rutz Claudia , Kreuchwig Annika , Krause Gerd , Simoni Manuela , Casarini Livio

The human luteinizing hormone (LH)/choriogonadotropin (hCG) receptor (LHCGR) discriminates its two hormone ligands. LHCGR differs to the murine receptor (Lhr) in aminoacid residues potentially involved in qualitative discerning of LH and hCG, the latter absent in rodents. We aim to identify LHCGR residues involved in hCG/LH discrimination, indicating evolutionary determinants of human LH/hCG endocrine system. After comparing the LHCGR and Lhr sequences, we developed eight ...

ea0081p455 | Reproductive and Developmental Endocrinology | ECE2022

Analysis of follicle-stimulating hormone receptor (FSHR)/g-protein coupled estrogen receptor (GPER) complex internalization through early and late endosomes

Lazzaretti Clara , Casadei Garofani Beatrice , Paradiso Elia , D'Alessandro Sara , Sperduti Samantha , Roy Neena , Mascolo Elisa , Baschieri Lara , Anzivino Claudia , Simoni Manuela , Casarini Livio

Introduction: Follicle-stimulating hormone (FSH) is a glycoprotein that support reproduction by regulating ovarian follicular growth and development. Recent studies demonstrated that proliferative signals mediating folliculogenesis are mediated by the G protein-coupled estrogen receptor (GPER) expressed in ovarian tissues throughout the follicular phase. In granulosa cells, GPER forms heteromers with FSHR, reprogramming cAMP-induced death signals to AKT-dependent, anti-apoptot...

ea0081p489 | Thyroid | ECE2022

cGMP is not involved in thyroid cancer cell death

D'Alessandro Sara , Paradiso Elia , Lazzaretti Clara , Sperduti Samantha , Baschieri Lara , Mascolo Elisa , Roy Neena , Anzivino Claudia , Righi Sara , Santi Daniele , Brigante Giulia , Simoni Manuela , Casarini Livio

Introduction: Type 5 phosphodiesterase (PDE5) inhibitors (PDE5i) lead to intracellular cyclic-guanosine monophosphate (cGMP) increase and are used for clinical treatment of erectile dysfunction. Studies found that cGMP may up/downregulate the growth of certain endocrine tumor cells, suggesting that the use of PDE5i could impact the risk of certain tumors, such as colorectal cancer.Aim: We evaluated if PDE5i may impact thyroid cancer cell growth in vi...

ea0090oc4.5 | Oral Communications 4: Reproductive and Developmental Endocrinology | ECE2023

Reprogramming of reproductive signals via human luteinizing hormone/choriogonadotropin receptor (LHCGR)/G protein-coupled estrogen receptor (GPER) heteromers

Lazzaretti Clara , Paradiso Elia , Sperduti Samantha , Sayers Niamh , Pelagatti Ginevra , D'Alessandro Sara , Perri Carmela , Baschieri Lara , Mascolo Elisa , Roy Neena , Simoni Manuela , Hanyaloglu Aylin , Casarini Livio

In the ovary, the G protein-coupled estrogen receptor (GPER) forms heteromeric complexes with the follicle-stimulating hormone receptor (FSHR), reprogramming FSH-induced signals and determining the follicular fate. Based on the structural similarity, we evaluated whether GPER interacts with the luteinizing hormone (LH)/choriogonadotropin (hCG) receptor (LHCGR) modulating gonadotropin-dependent signals. LHCGR-GPER heteromers were evaluated in transiently transfected HEK293 cell...