Searchable abstracts of presentations at key conferences in endocrinology

ea0037gp.09.02 | Nuclear receptors and signalling | ECE2015

Proliferative vs apoptotic signals in granulosa cells: β-arrestins as switch between life and death in vitro

Casarini Livio , Simoni Manuela

Background: The immortalised human granulosa cell line (hGL5) is not responding to gonadotropins, which fail to activate the cAMP/PKA/CREB pathway, progesterone production, cell rounding and apoptosis, suggesting that FSH- and LH/hCG-receptors (FSHR; LHCGR) are downregulated.Aim: To investigate whether the mechanism of FSHR/LHCGR downregulation is associated with life/death signals in hGL5 cells.Methods: We evaluated the FSHR/LHCGR...

ea0035p644 | Female reproduction | ECE2014

The PCOS evolutionary paradox: a GWAS-based, in silico, evolutionary explanation

Casarini Livio , Simoni Manuela

Introduction: PCOS is a common endocrine disorder in women exhibiting characteristics ranging from hyperandrogenic to metabolic phenotypes, more prevalent in people of African/Caucasian and Asian ancestry, respectively. Since PCOS impairs fertility without diminishing in prevalence, it was discussed as an evolutionary paradox. GWAS identified 17 SNPs with different allele frequencies, depending on ethnicity, in various susceptibility loci (FSHR, LHCGR, DENND1A, THADA, C9OR...

ea0049gp245 | Thyroid Cancer & Thyroid Case Reports | ECE2017

A statistical, in silico model predicts polygenic thyroid cancer risk

Casarini Livio , Marino Marco , Nuzzo Federico , Simoni Manuela , Brigante Giulia

Introduction: The detection of a unique genetic marker is not possible for multifactorial diseases, such as thyroid cancer (TC), where the pathological phenotype is given by the contribution of multiple genes, environmental factors and lifestyle. We found a mathematical model for inferring the risk of thyroid cancer, an example of multifactorial disease.Methods: Genetic data represented by 184 SNPs associated to thyroid tumors were used for Bayesian clus...

ea0049ep1107 | Female Reproduction | ECE2017

Efficacy of FSH alone, FSH + LH, hMG or FSH + hCG on ART outcomes in the ‘personalized’ medicine era: a meta-analysis

Santi Daniele , Casarini Livio , Alviggi Carlo , Simoni Manuela

Background: Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) act on the same receptor, activating different signal transduction pathways. The role of LH or hCG addition to follicle stimulating hormone (FSH) as well as menopausal gonadotropins (hMG) in controlled ovarian stimulation (COS) is debated.Aim: To compare FSH+LH, or FSH+hCG or hMG vs FSH alone on COS outcomes.Design: A meta-analysis according to PRISMA state...

ea0049ep1112 | Female Reproduction | ECE2017

Biological activity mediated by sfingosine-1-phospate receptors in human primary granulosa cells and immortalized granulosa cell line in vitro

Casarini Livio , Fornari Giulia , Simoni Manuela , Poti Francesco

Introduction: Sphingosine-1-phosphate (S1P) is a sphingolipid mediating proliferative signals in human ovarian follicles, acting through five receptors (S1PR1-5). We characterized the effects of S1PR1 and S1PR3 in vitro, as those mostly expressed in human primary granulosa cells (hGLC) and immortalized, tumor-like granulosa cell line (hGL5).Methods: The S1P-mediated signaling, as well as the activity of S1PR1- and S1PR3-specific agonists (SEW281...

ea0049ep1131 | Female Reproduction | ECE2017

The regulation of LHCGR-dependent signaling is linked to circadian gene expression

Gilioli Lisa , Marino Marco , Simoni Manuela , Casarini Livio

Introduction: Reproduction exhibit a regular cyclicity and is regulated by complex interactions between circadian signals, gonadotropins and sex steroid hormones. Peripheral circadian rhythm is generated upon cyclic transcription of clock genes expressed in several cells, e.g. granulosa cells in the ovary. Here we investigated whether cyclic intracellular events occurring in response to gonadotropins are linked to expression of clock genes.Methods: Prima...

ea0026p124 | Female reproduction | ECE2011

Two hormone for one receptors: dissecting out LH and hCG activity with an in vitro approach.

Casarini Livio , La Marca Antonio , Pignatti Elisa , Simoni Manuela

Introduction: LH and hCG act on the same receptor (LHCGR), have different half-lives and in vivo biopotency. It is not known whether they elicit the same cellular and molecular response. The aim of this study was to compare the kinetics of cAMP response to recombinant LH and hCG.Design: In COS-7 cells permanently expressing the human LHCGR (COS-7/LHCGR) we evaluated LH and hCG dose-response curves, by measuring total cAMP after 3 h of incubation. ...

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 & 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...

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...