Abstract:
:The human lutropin (hLH)/choriogonadotropin (hCG) receptor (LHCGR) can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG) - secreted by the placenta, and lutropin (LH) - produced by the pituitary. They induce different signaling profiles at the LHCGR. This cannot be explained by binding to the receptor's leucine-rich-repeat domain (LRRD), as this binding is similar for the two hormones. We therefore speculate that there are previously unknown differences in the hormone/receptor interaction at the extracellular hinge region, which might help to understand functional differences between the two hormones. We have therefore performed a detailed study of the binding and action of LH and CG at the LHCGR hinge region. We focused on a primate-specific additional exon in the hinge region, which is located between LRRD and the serpentine domain. The segment of the hinge region encoded by exon10 was previously reported to be only relevant to hLH signaling, as the exon10-deletion receptor exhibits decreased hLH signaling, but unchanged hCG signaling. We designed an advanced homology model of the hormone/LHCGR complex, followed by experimental characterization of relevant fragments in the hinge region. In addition, we examined predictions of a helical exon10-encoded conformation by block-wise polyalanine (helix supporting) mutations. These helix preserving modifications showed no effect on hormone-induced signaling. However, introduction of a structure-disturbing double-proline mutant LHCGR-Q303P/E305P within the exon10-helix has, in contrast to exon10-deletion, no impact on hLH, but only on hCG signaling. This opposite effect on signaling by hLH and hCG can be explained by distinct sites of hormone interaction in the hinge region. In conclusion, our analysis provides details of the differences between hLH- and hCG-induced signaling that are mainly determined in the L2-beta loop of the hormones and in the hinge region of the receptor.
journal_name
Front Endocrinol (Lausanne)journal_title
Frontiers in endocrinologyauthors
Grzesik P,Kreuchwig A,Rutz C,Furkert J,Wiesner B,Schuelein R,Kleinau G,Gromoll J,Krause Gdoi
10.3389/fendo.2015.00140subject
Has Abstractpub_date
2015-09-22 00:00:00pages
140issn
1664-2392journal_volume
6pub_type
杂志文章abstract::Background: The effect of testosterone supplementation in patients with chronic heart failure (CHF) remains uncertain. Methods: A meta-analysis of randomized controlled trials (RCTs) was performed. RCTs that evaluate the chronic effect of testosterone supplementation on exercise capacity and cardiac function in CHF we...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,meta分析
doi:10.3389/fendo.2020.00110
更新日期:2020-03-13 00:00:00
abstract::Background: Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder with heterogeneous manifestations and complex etiology. As a leading cause of anovulatory infertility, the molecular diversity of the follicular microenvironment has not been fully elucidated. The aim of the present study was to i...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00821
更新日期:2019-11-26 00:00:00
abstract::Introduction: To improve detection of undiagnosed diabetes in Africa, there is movement to replace the OGTT with A1C. The performance of A1C in the absence of hemoglobin-related micronutrient deficiencies, anemia and heterozygous hemoglobinopathies is unknown. Therefore, we determined in 441 African-born blacks living...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00533
更新日期:2019-08-07 00:00:00
abstract::Introduction: Secondary hyperparathyroidism (sHPT) is a common hormonal complication of chronic kidney disease. There are several therapeutic options for sHPT management aiming at calcium-phosphorus balance normalization and decrease of parathormone secretion. Objectives: The aim of this retrospective, observational s...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00040
更新日期:2019-02-05 00:00:00
abstract::Co-heritability of hypertension and insulin resistance (IR) within families not only implies genetic susceptibility may be responsible for these complex traits but also suggests a rational that biological candidate genes for hypertension may serve as markers for features of the metabolic syndrome (MetS). Thus we deter...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2013.00172
更新日期:2013-11-28 00:00:00
abstract::The insulin signaling pathway is a modulator of metabolism in insects and can regulate functions associated with growth and development, as well as lipid and carbohydrate balance. We have previously reported the presence of an insulin-like peptide and an insulin-like growth factor in Rhodnius prolixus, which are invol...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00745
更新日期:2018-12-06 00:00:00
abstract::Diabetes is a worldwide public health concern as it is associated with various complications. One of the major complications of diabetes is diabetic foot syndrome that results in catastrophic events such as ulceration and amputation. Therefore, the main four strategies of diabetic foot care involve risk prediction, pr...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2020.00308
更新日期:2020-05-22 00:00:00
abstract::The infertile patients with aging ovaries-also sometimes referred to as impending premature ovarian insufficiency (POI), impending premature ovarian failure (POF), or poor ovarian responders (POR), constitute a significant and increasing bulk of the patients appealing to IVF/ART. Different causes have been cited in th...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2020.00192
更新日期:2020-04-17 00:00:00
abstract::Congenital hyperinsulinism (CHI) is a heterogenous and complex disorder in which the unregulated insulin secretion from pancreatic beta-cells leads to hyperinsulinaemic hypoglycaemia. The severity of hypoglycaemia varies depending on the underlying molecular mechanism and genetic defects. The genetic and molecular cau...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00111
更新日期:2019-02-26 00:00:00
abstract::Germline development in vivo is dependent on the environment formed by somatic cells and the differentiation cues they provide; hence, the impact of local factors is highly relevant to the production of sperm. Knowledge of how somatic and germline cells interact is central to achieving biomedical goals relating to res...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2017.00307
更新日期:2017-11-20 00:00:00
abstract::Testosterone is responsible for several changes in the brain, including behavioral and emotional responses, memory, and cognition. Given this, we investigated changes in the brain wave profile caused by supplementation with exogenous testosterone in both castrated and non-castrated rats. We also investigated the serum...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00654
更新日期:2019-09-24 00:00:00
abstract::To investigate the expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) in the aorta of subclinical hypothyroidism (SCH) rat model. The mechanisms underlying thyrotropin (TSH) affecting eNOS and PGRN expression in human umbilical vein endothelial cells (HUVECs) cultured in vitro were investigat...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00353
更新日期:2018-07-05 00:00:00
abstract::Poor sleep and obesity are both extraordinarily common in the US adolescent population and often occur simultaneously. This review explores the links between obesity and sleep, outlining what is known about the relationships between sleep characteristics, obesity, and cardiometabolic risk factors in youth. Sleep durat...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2018.00364
更新日期:2018-07-10 00:00:00
abstract::The islet amyloid polypeptide (IAPP) or amylin maintains a key role in metabolism. This 37-residues-peptide could form pancreatic amyloids, which are a characteristic feature of diabetes mellitus type 2. However, some species do not form amyloid fibril structures. By employing a biomimetic approach, we generated an ex...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00331
更新日期:2018-06-25 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::Pituitary adenomas are common neoplasms. Their classification is based upon size, invasion of adjacent structures, sporadic or familial cases, biochemical activity, clinical manifestations, morphological characteristics, response to treatment and recurrence. Although they are considered benign tumors, some of them are...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2015.00097
更新日期:2015-06-12 00:00:00
abstract::A substantial body of evidence supports that the gut microbiota plays a pivotal role in the regulation of metabolic, endocrine and immune functions. In recent years, there has been growing recognition of the involvement of the gut microbiota in the modulation of multiple neurochemical pathways through the highly inter...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2020.00025
更新日期:2020-01-31 00:00:00
abstract::Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant disease, characterized by the formation of heterotopic ossification (HO) in muscles, ligaments, and tendons. Flare-ups, an inflammatory process that often precedes the formation of HO, can occur spontaneously, but trauma is also a common trigger. It ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.00006
更新日期:2020-02-12 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::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::Gastric cancer although occurring in reduced frequency is still an important disease, partly because of the bad prognosis when occurring in western countries. This decline in occurrence may mainly be due to the reduced prevalence of Helicobacter pylori (Hp) infection, which is the most important cause of gastric cance...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2017.00001
更新日期:2017-01-17 00:00:00
abstract::Over the last decades, thyroid hormone metabolites (THMs) received marked attention as it has been demonstrated that they are bioactive compounds. Their concentrations were determined by immunoassay or mass-spectrometry methods. Among those metabolites, 3,5-diiodothyronine (3,5-T2), occurs at low nanomolar concentrati...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00787
更新日期:2020-01-08 00:00:00
abstract::Background: The vast majority of pituitary tumors are benign and behave accordingly; however, a fraction are invasive and are more aggressive, with a very small fraction being frankly malignant. The cellular pathways that drive transformation in pituitary neoplasms are poorly characterized, and current classification ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00290
更新日期:2019-05-14 00:00:00
abstract::Background: Height is considered an indicator of health and well-being of an individual and population. Height variation results from a complex interaction of genetic, environmental, socioeconomic, and cultural influences. In order to understand the contribution of environmental stress associated with the child's grow...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.00106
更新日期:2020-03-11 00:00:00
abstract::The estrogen receptor and glucocorticoid receptor are members of the nuclear receptor superfamily that can signal using both non-genomic and genomic transcriptional modes. Though genomic modes of signaling have been well characterized and several behaviors attributed to this signaling mechanism, the physiological sign...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2015.00018
更新日期:2015-02-16 00:00:00
abstract::Calcium and bone homeostasis are intimately related. On the one hand, bone relies on a sufficient supply of calcium to maintain its structural and mechanical properties and thus largely depends on calcium absorption in the intestine and calcium reabsorption in the kidney. On the other hand, bone serves as a calcium re...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2012.00099
更新日期:2012-08-20 00:00:00
abstract::Background: Bologna criteria poor ovarian responders have a very low prognosis. Although, it has been proposed that LH supplementation could be beneficial in women with previous hypo-response to FSH. There are no studies comparing the cumulative live birth rates (LBRs) between corifollitropin alfa (CFA) and highly pur...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00175
更新日期:2019-03-22 00:00:00
abstract::The rapid increase of obesity rates worldwide is associated with chronic liver injury due to non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Chronic liver inflammation drives hepatic fibrosis, which is a highly conserved and coordinated protective response to tissue injury, and is a reversible pro...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2018.00455
更新日期:2018-08-21 00:00:00
abstract::McCune-Albright Syndrome (MAS; OMIM # 174800) is a rare, sporadic disease caused by a post-zygotic, activating mutation in the guanine-nucleotide binding protein α-subunit (GNAS1) gene. MAS is characterized by the clinical triad of polyostotic fibrous dysplasia of bone, café-au-lait skin pigmentation and peripheral pr...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2018.00337
更新日期:2018-06-22 00:00:00
abstract::Gonadotropin-inhibitory hormone (GnIH) was first identified in Japanese quail to be an inhibitor of gonadotropin synthesis and release. GnIH peptides have since been identified in all vertebrates, and all share an LPXRFamide (X = L or Q) motif at their C-termini. The receptor for GnIH is the G protein-coupled receptor...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2014.00008
更新日期:2014-01-27 00:00:00