Abstract:
:The orexigenic peptide hormone ghrelin is synthesized in the stomach and its receptor growth hormone secretagogue receptor (GHSR1a) is expressed mainly in the central nervous system (CNS). In this review, we confine our discussion to the physiological role of GHSR1a in the brain. Paradoxically, despite broad expression of GHSR1a in the CNS, other than trace amounts in the hypothalamus, ghrelin is undetectable in the brain. In our efforts to elucidate the function of the ligand-free ghrelin receptor (apo-GHSR1a), we identified subsets of neurons that co-express GHSR1a and dopamine receptors. In this review, we focus on interactions between apo-GHSR1a and dopamine-2 receptor (DRD2) and formation of GHSR1a:DRD2 heteromers in hypothalamic neurons that regulate appetite, and discuss implications for the treatment of Prader-Willi syndrome (PWS). GHSR1a antagonists of distinct chemical structures, a quinazolinone and a triazole, respectively, enhance and inhibit dopamine signaling through GHSR1a:DRD2 heteromers by an allosteric mechanism. This finding illustrates a potential strategy for designing the next generation of drugs for treating eating disorders as well as psychiatric disorders caused by abnormal dopamine signaling. Treatment with a GHSR1a antagonist that enhances dopamine/DRD2 activity in GHSR1a:DRD2 expressing hypothalamic neurons has the potential to inhibit the uncontrollable hyperphagia associated with PWS. DRD2 antagonists are prescribed for treating schizophrenia, but these block dopamine signaling in all DRD2 expressing neurons and are associated with adverse side effects, including enhanced appetite and excessive weight gain. A GHSR1a antagonist of structural class that allosterically blocks dopamine/DRD2 action in GHSR1a:DRD2 expressing neurons would have no effect on neurons expressing DRD2 alone; therefore, the side effects of DRD2 antagonists would potentially be reduced thereby enhancing patient compliance.
journal_name
Front Endocrinol (Lausanne)journal_title
Frontiers in endocrinologyauthors
Kern A,Grande C,Smith RGdoi
10.3389/fendo.2014.00129subject
Has Abstractpub_date
2014-08-18 00:00:00pages
129issn
1664-2392journal_volume
5pub_type
杂志文章,评审abstract::O-linked β-N-acetylglucosamine (O-GlcNAc) is an abundant and essential intracellular form of protein glycosylation in animals and plants. In humans, dysregulation of O-GlcNAcylation occurs in a wide range of diseases, including cancer, diabetes, and neurodegeneration. Since its discovery more than 30 years ago, great ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00606
更新日期:2018-10-15 00:00:00
abstract::Protease-activated receptors (PARs) belong to the G protein-coupled receptor (GPCR) family. Compared to other GPCRs, the specificity of the four PARs is the lack of physiologically soluble ligands able to induce their activation. Indeed, PARs are physiologically activated after proteolytic cleavage of their N-terminal...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00717
更新日期:2019-10-24 00:00:00
abstract::Objective: To clarify the role and mechanism of miR-17-92 cluster in islet beta-cell repair after streptozotocin intervention. Methods: Genetically engineered mice (miR-17-92βKO) and control RIP-Cre mice were intraperitoneally injected with multiple low dose streptozotocin. Body weight, random blood glucose (RBG), fas...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.00009
更新日期:2020-01-23 00:00:00
abstract::We sought to determine the efficacy of 12 weeks high-intensity interval training (HIIT), compared to moderate-intensity continuous training (MICT) on glucose control, cardiometabolic risk and microvascular complication markers in men living with type 2 diabetes (T2D). Both modalities were combined with resistance trai...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00475
更新日期:2018-08-28 00:00:00
abstract::Follicle stimulating hormone (FSH) plays a key role in human reproduction through, among others, induction of spermatogenesis in men and production of estrogen in women. The function FSH is performed upon binding to its cognate receptor-follicle-stimulating hormone receptor (FSHR) expressed on the surface of target ce...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2018.00760
更新日期:2018-12-13 00:00:00
abstract::Microtubule-associated protein tau assists in stabilizing microtubules and has been particularly implicated in Alzheimer's disease (AD). Given the importance of tau to AD pathogenesis and therapies, it is important to understand non-classic physiological functions for this protein inside and outside the central nervou...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.00124
更新日期:2020-03-12 00:00:00
abstract:Objective:Both vitamin D and K2 are involved in a number of metabolic processes, including bone metabolism; however, associations between the vitamins are not fully understood. The aim of the study was to evaluate serum concentrations of 25-hydroxyvitamin D [25(OH)D] in adult patients receiving long-term acenocoumarol ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00226
更新日期:2018-05-04 00:00:00
abstract::Graves' Orbitopathy (GO) is the most frequent extrathyroidal manifestation of Graves' disease (GD). Its ultimate cause remains unclear, but it is commonly considered an autoimmune disorder due to self recognition of autoantigens constitutively expressed by orbital fibroblasts (OFs), and thyroid epithelial cells. High ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00933
更新日期:2020-01-22 00:00:00
abstract::Some newly described steroid-related compounds, also found in the rest of the body, are formed and active in the central nervous system, particularly in the brain. Some are of pharmacological and physiopathological interest. We specifically report on two compounds, "MAP4343," a new neurosteroid very efficient antidepr...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00316
更新日期:2018-06-15 00:00:00
abstract::Growth hormone (GH) has been used as an adjunct in the field of female infertility treatment for more than 25 years, although, apart from treating women with GH deficiency its role has not yet been clarified. Contributing to this lack of clarity is that several underpowered studies have been performed on women undergo...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00500
更新日期:2019-07-24 00:00:00
abstract::Background: IL-36α is involved in the pathogenesis of a variety of autoimmune diseases, but the relationship between IL-36α and Graves' disease (GD) has rarely investigated. In the present study, we aimed to explore the expression of IL-36α and elucidate the potential role of IL-36α in GD. Methods: The expression of I...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00591
更新日期:2018-10-09 00:00:00
abstract::Spontaneous and oxytocin induced contractile activity was quantified in the bicornuate uteri of pregnant rabbits maintained in situ, using data from two- and uni- dimensional video spatiotemporal maps (VSTM) of linear and area strain rate and compared statistically. Spontaneous contractions occurred over a range of fr...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00802
更新日期:2019-11-21 00:00:00
abstract::Sleep duration has become increasingly recognized as an important influencer of health. Epidemiologic and observational studies have shown associations between short sleep duration and increased risk for chronic cardiometabolic disorders, including obesity, type 2 diabetes, and cardiovascular disease. These associatio...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2018.00392
更新日期:2018-07-18 00:00:00
abstract::The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00196
更新日期:2018-04-26 00:00:00
abstract::This review focuses on the biologic importance of the vitamin D binding protein (DBP) with emphasis on its regulation of total and free vitamin D metabolite levels in various clinical conditions. Nearly all DBP is produced in the liver, where its regulation is influenced by estrogen, glucocorticoids and inflammatory c...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00317
更新日期:2019-05-28 00:00:00
abstract::Background: Gestational diabetes (GDM) is associated with adverse short- and long-term maternal and fetal outcomes. Observational data support a link between sleep-disordered breathing (SDB) during pregnancy and GDM. However, it is unknown whether treatment of SDB with continuous positive airway pressure (CPAP) improv...
journal_title:Frontiers in endocrinology
pub_type:
doi:10.3389/fendo.2018.00659
更新日期:2018-11-16 00:00:00
abstract::[This corrects the article DOI: 10.3389/fendo.2019.00276.]. ...
journal_title:Frontiers in endocrinology
pub_type: 已发布勘误
doi:10.3389/fendo.2019.00405
更新日期:2019-06-26 00:00:00
abstract::Breast cancer (BC) is one of the most common malignancies and the leading cause of cancer-related mortality in women. Androgen receptor (AR) is frequently expressed in diverse BC subtypes. Accumulating evidence has revealed that AR might be a predictive or prognostic factor and a drug target in BC. AR expression and A...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2020.00573
更新日期:2020-09-02 00:00:00
abstract::Cardiovascular disease (CVD) is the leading cause of death globally. It is well-established based on evidence accrued during the last three decades that high plasma concentrations of cholesterol-rich atherogenic lipoproteins are causatively linked to CVD, and that lowering these reduces atherosclerotic cardiovascular ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2020.00474
更新日期:2020-07-28 00:00:00
abstract::Polycystic ovary syndrome (PCOS) is the commonest endocrine abnormality in women of reproductive age typically presenting with chronic oligo- or anovulation, clinical, or biochemical hyperandrogenism and polycystic ovarian morphology (PCOM). Restoring mono-ovulation is the ultimate goal of ovulation induction and most...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00023
更新日期:2019-02-12 00:00:00
abstract::Background: Amiodarone-induced thyrotoxicosis (AIT) is associated with significant morbidity and mortality, particularly in patients with cardiac failure. The aim of the study was to evaluate the management of AIT at a tertiary hospital specialising in cardiac failure and transplantation. Methods: Retrospective audit ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00482
更新日期:2018-08-22 00:00:00
abstract::The relaxin-like RXFP1 ligand-receptor system has important functions in tumor growth and tissue invasion. Recently, we have identified the secreted protein, CTRP8, a member of the C1q/tumor necrosis factor-related protein (CTRP) family, as a novel ligand of the relaxin receptor, RXFP1, with functions in brain cancer....
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2015.00127
更新日期:2015-08-13 00:00:00
abstract::The increase of life expectancy has led to the increase of age-related diseases such as osteoporosis. Osteoporosis is characterized by bone weakening promoting the occurrence of fractures with defective bone regeneration. Men aged over 50 have a prevalence for osteoporosis of 20%, which is related to a decline in sex ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2015.00081
更新日期:2015-05-19 00:00:00
abstract::The insulin/IGF system plays an important role in cancer progression. Accordingly, elevated levels of circulating insulin have been associated with an increased cancer risk as well as with aggressive and metastatic cancer phenotypes. Numerous studies have documented that estrogens cooperate with the insulin/IGF system...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2015.00030
更新日期:2015-03-06 00:00:00
abstract::In mammals, glucosensing markers reside in brain areas known to play an important role in the control of food intake. The best characterized glucosensing mechanism is that dependent on glucokinase (GK) whose activation by increased levels of glucose leads in specific hypothalamic neurons to decreased or increased acti...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00254
更新日期:2019-04-18 00:00:00
abstract::Introduction: We have previously shown that fetuses of mothers with gestational diabetes mellitus (GDM) and insulin resistance exhibit a prolongation of fetal auditory event-related brain responses (fAER) compared to fetuses of normal glucose tolerant women during an oral glucose tolerance test (oGTT). This implies th...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00673
更新日期:2018-11-20 00:00:00
abstract::Background: In the past decade, continuous glucose monitoring (CGM) has been proven to have similar accuracy to self-monitoring of blood glucose (SMBG) and yet provides better therapy optimization and detects trends in glucose values due to higher frequency of testing. Even though the feasibility and utility of CGM ha...
journal_title:Frontiers in endocrinology
pub_type:
doi:10.3389/fendo.2019.00697
更新日期:2019-10-11 00:00:00
abstract::Background: The relative contribution of reduced insulin sensitivity (Si) or insulin secretion to impaired fasting glucose (IFG) or diabetes mellitus (DM) has not been clarified in active acromegaly. An intravenous glucose tolerance test (IVGTT) was never used for the calculation of Si, acute insulin response (AIRg), ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00637
更新日期:2019-09-18 00:00:00
abstract::Accumulating evidence shows that H2S has physiological functions in various tissues and organs. It includes regulation of neuronal activity, vascular tension, a release of insulin, and protection of the heart, kidney, and brain from ischemic insult. H2S is produced by enzymes from l-cysteine; cystathionine β-synthase,...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2013.00087
更新日期:2013-07-16 00:00:00
abstract::Obstructive sleep apnea-hypopnea syndrome (OSAHS) is frequently present in patients with severe obesity, but its prevalence especially in women is not well defined. OSAHS and non-alcoholic fatty liver disease are common conditions, frequently associated in patients with central obesity and metabolic syndrome and are b...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00293
更新日期:2018-06-06 00:00:00