Searchable abstracts of presentations at key conferences in endocrinology

ea0037ep168 | Reproduction, endocrine disruptors and signalling | ECE2015

Heterogeneity of human chorionic gonadotropin (hCG) in commercial preparations of hCG and human menopausal gonadotropin

Riccetti Laura , Pignatti Elisa , Simoni Manuela

Introduction: Human chorionic gonadotropin (hCG) is a glycoprotein hormone composed by two subunits, an alpha subunit common to all gonadotropins and a specific beta subunit. hCG is produced by trophoblast cells as differently glycosylated isoforms with a wide range of molecular weight, from 30 to 50 KDa (‘regular’ hCG is 37 KDa). hCG is used in the treatment of infertility. The aim of this study is to analyse and compare the composition of different commercial hCG.<...

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...

ea0041gp176 | Receptors &amp; Signalling | ECE2016

Luteinizing hormone and human chorionic gonadotropin (hCG) action on the same receptor results in different in vitro intracellular signaling in mouse primary Leydig cells

De Pascali Francesco , Riccetti Laura , Poti Francesco , Tagliavini Simonetta , Trenti Tommaso , Simoni Manuela , Casarini Livio

Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are two glycoprotein hormones regulating development and reproduction. Despite binding the same receptor (LHCGR), they elicit different intracellular signaling. In vitro non-equivalence of hCG and LH was previously demonstrated in human primary granulosa cells. The aim of this study is to compare the effects of LH and hCG in mouse primary Leydig cells in vitro, naturally expressing the murine rec...

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...

ea0041oc10.2 | Reproduction &amp; 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 &amp; 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)...

ea0063p645 | Interdisciplinary Endocrinology 1 | ECE2019

Demonstration of follicle-stimulating hormone receptor (FSHR) and G protein-coupled estrogen receptor (GPER) heterodimerization by bioluminescence resonance energy transfer (BRET)

Lazzaretti Clara , Paradiso Elia , Riccetti Laura , Sperduti Samantha , Brigante Giulia , Poti Francesco , Fanelli Francesca , Simoni Manuela , Hanyaloglu Aylin Carla , Casarini Livio

During the menstrual cycle, selection of the dominant follicle is characterized by changes of gonadotropin and steroid hormone receptor expression. We aim to evaluate whether co-existing follicle-stimulating hormone receptor (FSHR) and G protein-coupled estrogen receptor (GPER) form heterodimers, suggesting their role in ovarian follicle selection. FSHR-GPER dimerization was evaluated in transfected HEK293 cells in vitro by bioluminescence resonance energy transfer (B...

ea0063p646 | Interdisciplinary Endocrinology 1 | ECE2019

Spingosine-1-phosphate induces cAMP/PKA-independent pCREB activation, but not steroidogenesis, in human granulosa cells

Paradiso Elia , Lazzaretti Clara , Riccetti Laura , Sperduti Samantha , Antoniani Francesco , Brigante Giulia , Feo Gaetano De , Morini Daria , Iannotti Francesca , Simoni Manuela , Poti Francesco , Casarini Livio

Sphingosine-1 phosphate (S1P) is a lysosphingolipid present in the ovarian follicular fluid at the nanomolar concentration. The physiological functions of S1P are mediated through five specific G protein-coupled receptors (GPCRs), known as S1PR1-5. S1PR1 and S1PR3 are expressed in human primary granulosa lutein cells (hGLC), as well as in the immortalized human primary granulosa cell line hGL5. S1PRs are activated at nanomolar concentrations inducing specific activation or inh...

ea0063p644 | Interdisciplinary Endocrinology 1 | ECE2019

Dominance of ovarian follicles is determined by follicle-stimulating hormone receptor (FSHR) and G protein-coupled estrogen receptor (GPER) heteromers

Casarini Livio , Lazzaretti Clara , Paradiso Elia , Riccetti Laura , Sperduti Samantha , Marcozzi Serena , Sayers Niamh , Brigante Giulia , Poti Francesco , La Marca Antonio , Valli Barbara , Falbo Angela , Villani Maria Teresa , Klinger Francesca Gioia , Fane Francesca , Hanyaloglu Aylin Carla , Simoni Manuela

Mechanisms regulating the selection of antral ovarian follicles are poorly understood and supposed to rely on low estrogen levels, decline of follicle-stimulating hormone (FSH) levels and receptor (FSHR) expression on the surface of granulosa cells. These concepts are challenged in-vitro, where apoptosis of human granulosa cells (hGLC) and transfected cell lines is induced by high doses of FSH or FSHR overexpression, while estrogens induce anti-apoptotic signals via n...