Endocrine Abstracts

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...

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...

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...

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...

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 ...

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...

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...

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 ...

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...

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...