Searchable abstracts of presentations at key conferences in endocrinology

ea0041oc10.2 | Reproduction & Endocrine Disruption | ECE2016

Human luteinizing hormone (hLH) and chorionic gonadotropin (hCG) display biased agonism at the LH/CG receptor

Riccetti Laura , Akli Ayoub Mohammed , Klett Daniele , Yvinec Romain , Gallay Nathalie , Combarnous Yves , Casarini Livio , Simoni Manuela , Reiter Eric

Human luteinizing hormone (LH) and human choriogonadotropin (hCG) were considered biologically equivalent for decades due to structural similarities and binding to the same receptor (LHCGR). However, LHCGR triggers differential, LH- and hCG-specific, cAMP production, steroidogenesis, ERK and AKT activation and gene expression in granulosa cells. Besides the Gs/cAMP/PKA pathway, hCG and LH bioactivity on β-arrestin- and Gq/PLC-dependent pathways are yet to be determined. W...

ea0041gp186 | Reproduction & Endocrine Disruption | ECE2016

FSH increases the different LH- and hCG-dependent intracellular signalling and the downstream life/death signals in vitro

Casarini Livio , Riccetti Laura , De Pascali Francesco , Nicoli Alessia , Tagliavini Simonetta , Trenti Tommaso , Battista La Sala Giovanni , Simoni Manuela

Background: Luteinizing hormone (LH) and choriogonadotropin (hCG) are glycoprotein hormones regulating ovarian function and pregnancy. They were routinely used in assisted reproduction techniques (ART) assuming they are equivalent, due to their binding to a common receptor (LHCGR). However, differences between LH and hCG were demonstrated at molecular and physiological level.Aim: The aim of this study is to evaluate how follicle-stimulating hormone (FSH)...

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 ...

ea0070aep880 | Thyroid | ECE2020

Clinical practice survey on BRAF V600E role in the therapeutic decision in indeterminate thyroid cytology

Brigante Giulia , Craparo Andrea , Pignatti Elisa , Marino Marco , Casarini Livio , Sperduti Samantha , Boselli Gisella , Margiotta Gianluca , Rochira Vincenzo , Simoni Manuela

Introduction: The use of multigene panels in thyroid nodule diagnosis is still limited, due to high costs and need for ad hoc sampling. Since BRAF-V600E is the commonest genetic alteration in differentiated thyroid cancer, this is the mostly tested genetic parameter in clinical practice.Aim: To evaluate the use of BRAF mutation analysis in wash-out liquid from fine needle aspiration (FNA) in clinical practice, characterizing th...

ea0099p385 | Thyroid | ECE2024

hCG-TSHR cross-interaction: a rationale for in hyperemesis gravidarum?

Perri Carmela , Lazzaretti Clara , Baschieri Lara , Marchetti Lorenzo , Sperduti Samantha , Fusco Claudia , Simoni Manuela , Brigante Giulia , Casarini Livio

About 50% of women have nausea and vomiting during pregnancy. In about 35% of women who have these symptoms, nausea and vomiting are clinically significant, worsening their living conditions and consisting in a case of gender gap. The severe form, hyperemesis gravidarum, ranges from 0.3 to 1.0% of cases and is characterized by persistent vomiting, gestational thyrotoxicosis, weight loss of more than 5%, ketonuria, hypokalemia and dehydration, although the pathophysiological me...

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...

ea0090rc2.5 | Rapid Communications 2: Thyroid | ECE2023

Lack of GPER-TSHR heteromers is a hallmark of thyroid cancer

Perri Carmela , D'Alessandro Sara , Paradiso Elia , Lazzaretti Clara , Mascolo Elisa , Baschieri Lara , Roy Neena , Sperduti Samantha , Simoni Manuela , Brigante Giulia , Casarini Livio

Thyroid cancer is the most common type of endocrine tumor and reaches the peak of incidence between the age of twenty and fifty years. It has 4-fold higher prevalence in females than males, suggesting that estrogens and their receptors could be involved in thyroid cancer pathogenesis. Previous studies demonstrated allosteric interference operated by G protein-coupled estrogen receptor (GPER) to molecules structurally similar to the thyroid-stimulating hormone (TSH) receptor (T...

ea0090p443 | Reproductive and Developmental Endocrinology | ECE2023

Protein kinase B (Akt) blockade inhibits LH/hCG-mediated 17,20-lyase, but not 17α-hydroxylase activity of CYP17a1 in mouse Leydig cell steroidogenesis

Paradiso Elia , Lazzaretti Clara , Sperduti Samantha , Melli Beatrice , Perri Carmela , D'Alessandro Sara , Baschieri Lara , Mascolo Elisa , Roy Neena , Simoni Manuela , Casarini Livio

Androgens are sex steroid hormones fundamental for human reproduction. In males, they are produced upon luteinizing hormone (LH) action through its specific receptor (LHCGR) expressed in Leydig cells, supporting spermatogenesis. The human chorionic gonadotropin (hCG), acting on the same receptor but not expressed in men, is administered to improve testosterone synthesis in specific pathological contexts, such as hypogonadotropic hypogonadism and cryptorchidism. In vitro</e...