Searchable abstracts of presentations at key conferences in endocrinology

ea0056p980 | Pituitary - Basic | ECE2018

In vitro characterization and comparison of commercial GnRH antagonists

Sperduti Samantha , Riccetti Laura , Lazzaretti Clara , Simoni Manuela , Casarini Livio

Introduction: Hypothalamic gonadotropin releasing hormone (GnRH) regulates mammalian reproductive system. It binds receptors (GnRHRs) expressed in gonadotrope cells of anterior pituitary, regulating the synthesis and secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). GnRHR is a G protein-coupled receptor (GPCR) coupled to Gαq/11 protein and, to a lesser extent, to Gαi/Gαs proteins, simultaneously activating Ca2+, β-cate...

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...

ea0056gp220 | Reproduction | ECE2018

Depletion of the primate-specific luteinizing-hormone receptor splice variant ‘exon-6A’ impairs LH-, but not hCG-mediated signaling in human primary granulosa cells

Casarini Livio , Riccetti Laura , Sperduti Samantha , Lazzaretti Clara , Masini Alessia , Simoni Manuela

Introduction: A primate-specific luteinizing hormone (LH) receptor (LHCGR)-variant was suspected to discriminate between maternal choriogonadotropin (hCG)- and fetal LH-functioning. It is the so-called “LHCGRex6A”, truncated, intracellular receptor isoform produced by alternative cryptic exon stop-codons located between the 6th-7th out of 11 exons. Its function is unknown, although pseudohermaphroditism and 46-XY female-like phenotype were associated with LHCGRex...

ea0056p942 | Female Reproduction | ECE2018

Recombinant FSH and biosimilars result in different intracellular signaling

Riccetti Laura , Sperduti Samantha , Lazzaretti Clara , Tagliavini Simonetta , Simoni Manuela , Casarini Livio

Introduction: Follicle-stimulating hormone (FSH) biosimilars, differing for source cell and glycosylation pattern, are commercially available for therapy of hypogonadism and assisted reproduction techniques (ART). Although these molecules are commonly used in clinical practice, comparison of their action in vitro was poorly investigated.Aim: The aim of the study is to compare recombinant FSH- and biosimilars-induced cell response in vitro</e...

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 ...