Searchable abstracts of presentations at key conferences in endocrinology

ea0065p177 | Metabolism and Obesity | SFEBES2019

Investigating the role of GPR119 in the vagus nerve

Cheng Sijing , Roberts Anna , Norton Mariana , Owen Bryn , Hanyaloglu Aylin , Murphy Kevin

The prevalence of obesity and its associated metabolic diseases are increasing, but current treatments are ineffective or impractical. Understanding how the gut–brain axis senses nutrients to regulate appetite and glucose homeostasis may identify new drug targets and treatments. The G protein-coupled receptor 119 (GPR119) has several endogenous lipid ligands and has been proposed to act as a nutrient sensor in the gastrointestinal tract. GPR119 is expressed on enteroendoc...

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...

ea0031s9.3 | Novel aspects of GPCR signalling (Supported by the <emphasis role="italic">Journal of Endocrinology</emphasis>) | SFEBES2013

In vivo dimerization of LH receptors

Rivero-Muller Adolfo , Jonas Kim , Trehan Ashutosh , Hanyaloglu Aylin , Huhtaniemi Ilpo

The classical model of GPCR activation entails the binding of a single ligand to a single receptor molecule, followed by transmembrane signal transduction to the appropriate G protein(s). The possibility of GPCRs functioning as dimers or oligomers still remains controversial, and is largely based on in vitro studies on transfected cells. The glycoprotein hormone receptors, including that of LH (LHCGR), differ from most GPCRs by their large extracellular ligand-binding...

ea0031oc3.1 | Reproduction, growth and development | SFEBES2013

Identification of very early sorting endosomes that spatially program gonadotrophin hormone receptor signalling

Jean-Alphonse Frederic , Bowersox Shanna , Chen Stanford , Beard Gemma , Puthenveedu Manojkumar , Hanyaloglu Aylin

G protein-coupled receptors (GPCRs) are one of the largest families of the mammalian genome and represent the single most common therapeutic target. The glycoprotein hormones; LH and human chorionic gonadotrophin, act at a single GPCR the LH/hCGR, whose roles in reproductive function and pregnancy are well known. Endocytic trafficking of GPCRs represents a key mechanism in defining cellular responses in complex signaling pathways by controlling both the temporal and spatial pa...

ea0031oc3.3 | Reproduction, growth and development | SFEBES2013

Regulation of G protein-coupling specificity via cis and trans activation of the LH/chorionic gonadotrophin receptor (LHCGR)

Jonas Kim , Muller Adolfo Rivero , Chou Yen Yin , Ji Tae , Hanyaloglu Aylin

Accepted dogma once stated that G protein-coupled receptors (GPCRs) function as monomers, however, over the last decade in vitro experiments have shown GPCRs to function as dimers and higher order oligomers. We have recently reported the first in vivo evidence for the physiological importance of Class A GPCR homodimerisation using the LHCGR as a model receptor. Transgenic co-expression of binding deficient LHCGR (LHCGR-LH) and signalling deficient ...

ea0028p279 | Reproduction | SFEBES2012

Dimerisation of luteinising hormone/chorionic gonadotrophin receptor (LHCGR); impact on intracellular signaling responses and ligand specificity

Jonas Kim , Rivero-Muller Adolfo , Chou Yen-Yin , Ji Tae , Hanyaloglu Aylin , Huhtaniemi Ilpo

G protein-coupled receptors (GPCRs) are one of the largest families of the mammalian genome, mediating the effects of approximately 40% of prescribed drugs. Until recently, accepted dogma stated that GPCRs exist as monomers, however, it is becoming evident that GPCRs can form higher order dimer/oligomer complexes which provide important mechanisms for the diversification of receptor function. The LHCGR is a class A family GPCR, primarily coupling to the Gαs pat...

ea0056gp130 | Female Reproduction | ECE2018

Alterations in gonadotropin receptors and signal activation in granulosa lutein cells from women with polycystic ovary syndrome

Owens Lisa , Christopolous Georgios , Khanjani Shirin , Hardy Kate , Lavery Stuart , Franks Stephen , Hanyaloglu Aylin

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 5–10% of women of reproductive age. The underlying pathogenesis is complex and incompletely understood. There is evidence that gonadotropin and gonadotropin receptor action play a role in the pathogenesis of PCOS with genome wide association studies in PCOS also implicating altered gonadotropin action in the aetiology of PCOS. Furthermore, our recent studies have demonstrated that gonad...

ea0073s13.2 | Symposium 13: TGF-β signalling in ovaries in women with PCOS | ECE2021

LH-receptor activity and interaction with TGF-β family members in women with PCOS

Owens Lisa , Kristensen Stine Gry , Lerner Avi , Hanyaloglu Aylin , Hardy Kate , Andersen Claus Yding , Franks Stephen

The luteinising hormone/chorionic gonadotropin receptor (LHCGR) plays an essential role in ovarian follicular function, mediating the action of LH on theca cell steroidogenesis and, in the preovulatory follicle, on granulosa cell (GC) steroid production and the ovulatory cascade. Following ovulation, LH (and CG) are responsible for maintenance and function of the corpus luteum. Arrested antral follicle development in PCOS is characterised by premature responsiveness of GCs to ...

ea0094oc4.5 | Reproductive Endocrinology | SFEBES2023

Luteinising hormone receptor signalling is reliant on formation of distinct multi-receptor complexes

Walker Abigail , Hopkins Thomas , Howell Lesley , Farooq Zara , McCormick Peter , Jonas Kim , Hanyaloglu Aylin

Luteinising hormone (LH) and the luteinising hormone receptor (LHR) have key roles in steroidogenesis and ovulation, thus are central targets for fertility treatment. The LHR is a G protein-coupled receptor that predominantly signals through Gαs, although under conditions of high ligand concentration and/or high receptor density, as occurs during the mid-cycle LH surge, can also signal via Gαq/11. Yet, how LHR delineates signal pathway activation to coordinate pleiot...

ea0094p264 | Reproductive Endocrinology | SFEBES2023

Insights into dysregulation of luteinizing hormone receptor (LHR) signaling in granulosa lutein (GL) cells from women with polycystic ovary syndrome (PCOS)

Anujan Priyanka , Owens Lisa , Talwar Divreena , Hardy Kate , Hanyaloglu Aylin , Franks Stephen

Polycystic ovary syndrome (PCOS) is a multifactorial, complex endocrine disorder affecting a significant proportion of the global population. Aberrant secretion and/or action of gonadotropins is implicated in PCOS, but, to date, we have only limited knowledge about the precise mechanisms involved. We therefore studied LHR expression, signalling and trafficking in GLCs from women with and without PCOS. GLCs from women with PCOS exhibited enhanced Gαs-cAMP signalling respon...