Abstract:
OBJECTIVE:The molecular mechanisms of TSH receptor (TSHR) activation and intramolecular signal transduction are largely unknown. Deletion of the extracellular domain (ECD) of the TSHR results in increased constitutive activity, which suggests a self-inhibitory interaction between the ECD and the extracellular loops (ECLs) or the transmembrane domains (TMDs). To investigate these potential interactions and to pursue the idea that mutations in the ECD affect the constitutive activity of mutants in the ECLs or TMDs we generated double mutants between position 281 in the ECD and mutants in all three ECLs as well as the 6th TMD. DESIGN:We combined mutation S281D, characterized by an impaired TSH-stimulated cAMP response, with the constitutively activating in vivo mutations I486F (1st ECL), I568T (2nd ECL), V656F (3rd ECL) and D633F (6th TMD). Further, we constructed double mutants containing the constitutively activating mutation S281N and one of the inactivating mutations D474E, T477I (1st ECL) and D633K (6th TMD). RESULTS:The cAMP level of the double mutants with S281N and the inactive mutants in the 1st ECL was decreased below the level of the inactive single mutants, demonstrating that a constitutively activating mutation in the ECD cannot bypass disruption of signal transduction in the serpentine domain. In double mutants with S281D, basal and TSH-induced cAMP and inositol phosphate production of constitutively active mutants was reduced to the level of S281D. CONCLUSION:The dominance of S281D and the dependence of constitutively activating mutations in the ECLs on the functionally intact ECD strongly suggest that interactions between these receptor domains are required for TSHR activation and intramolecular signal transduction.
journal_name
Eur J Endocrinoljournal_title
European journal of endocrinologyauthors
Neumann S,Claus M,Paschke Rdoi
10.1530/eje.1.01891subject
Has Abstractpub_date
2005-04-01 00:00:00pages
625-34issue
4eissn
0804-4643issn
1479-683Xpii
152/4/625journal_volume
152pub_type
杂志文章abstract:OBJECTIVE:Serum concentrations of soluble tumor necrosis factor-alpha (TNF-alpha) receptor 2 (sTNFR2) are associated with insulin resistance. In a recent study, we provided evidence for the existence of a biologically active form of sTNFR2 produced by alternative splicing (DS-TNFR2). We aimed to evaluate whether this c...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.02145
更新日期:2006-05-01 00:00:00
abstract::This is a brief review of the normal changes in adolescent behaviour and the interplay between biology and social factors that occur at and around puberty, in an attempt to explain when this transition may become problematic The onset of puberty is a biological marker for an individual's transition from a non-reproduc...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/eje.0.151u151
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:Previous studies have suggested that infections are an important cause of death in patients with Addison's disease, but epidemiological studies on the frequency of infections in this population are lacking. OBJECTIVE:To assess and compare the incidence risk of infections in patients with primary adrenal ins...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-12-0879
更新日期:2013-03-15 00:00:00
abstract:BACKGROUND:A limited number of mutations in the GH secretagogue receptor gene (GHSR) have been described in patients with short stature. Objective To analyze GHSR in idiopathic short stature (ISS) children including a subgroup of constitutional delay of growth and puberty (CDGP) patients. SUBJECTS AND METHODS:The GHSR...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-11-0168
更新日期:2011-08-01 00:00:00
abstract:OBJECTIVE:Chromosomal rearrangements of the RET proto-oncogene is one of the most common molecular events in papillary thyroid carcinoma (PTC). However, their pathogenic role and clinical significance are still debated. This study aimed to investigate the prevalence of RET/PTC rearrangement in a cohort of BRAF WT PTCs ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-14-0930
更新日期:2015-05-01 00:00:00
abstract::Male age-related bone loss is caused, at least in part, by hypogonadism that occurs with advancing age. The study of the effects of sex steroids on bone physiology in men has recently highlighted the central role of estrogens on bone pathophysiology. This review focuses on particular aspects of bone physiology and pat...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/eje.1.02088
更新日期:2006-02-01 00:00:00
abstract:INTRODUCTION:In an animal model of acromegaly (PEPCK-hGH transgenic mice), low systemic levels of ghrelin have been observed compared with normal mice. We hypothesized that systemic circulating ghrelin levels are also decreased in humans with active acromegaly and that the contribution of central ghrelin production to ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1470195
更新日期:2002-08-01 00:00:00
abstract::Sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) levels were evaluated in euthyroid (N = 111), hyper- (N = 58) and hypothyroid (N = 38) men, in pre- and postmenopausal women (study 1) and in hyper- (N = 24) and hypothyroid (N = 15) patients before and after treatment with carbimazole or le...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1320594
更新日期:1995-05-01 00:00:00
abstract:OBJECTIVE:Previous evidence has suggested that a low sex hormone-binding globulin (SHBG) concentration is associated with insulin-resistance and a low adiponectin concentration. We investigated the association between SHBG and the risk of hyperglycemia in each sex and we determined potential interactions between SHBG a...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0202
更新日期:2009-07-01 00:00:00
abstract:CONTEXT:Acromegaly is a rare disease associated with chronic multisystem complications. National registries have been created in several countries. DESIGN:The French Registry contains data on acromegaly epidemiology, management and comorbidities recorded over more than three decades, retrospectively until 1999 and pro...
journal_title:European journal of endocrinology
pub_type: 杂志文章,多中心研究
doi:10.1530/EJE-16-1064
更新日期:2017-05-01 00:00:00
abstract:UNLABELLED:In healthy boys, the pituitary-gonadal axis exhibits diurnal variation in early puberty. Serum testosterone levels are higher during the night and low or immeasurable during the day. These fluctuating levels of circulating androgens in early pubertal boys are difficult to monitor. Prostate specific antigen (...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1360401
更新日期:1997-04-01 00:00:00
abstract:BACKGROUND:Ghrelin is a peptide mainly secreted by gastric mucosa and has been implicated in the regulation of eating behavior and weight balance. Obesity and Helicobacter pylori infection are associated with changes in plasma ghrelin levels. OBJECTIVE:This study was designed to evaluate the density of ghrelin-produci...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-11-0201
更新日期:2011-07-01 00:00:00
abstract::The aim of this review was to examine the evidence for age-related changes of the hypothalamic-pituitary-adrenal (HPA) axis in both physiological and pathological aging, on the basis of the many data in the literature, as well as of our personal findings. A statistically significant circadian rhythmicity of serum cort...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/eje.0.1440319
更新日期:2001-04-01 00:00:00
abstract:BACKGROUND:Lithium, clinically used in the treatment of bipolar disorders, is well known to induce thyroid growth. However, the mechanism involved is only incompletely characterized. Although it is conventionally believed that thyroid proliferation depends on the thyroid-stimulating hormone (TSH)/cAMP/cAMP response ele...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.02038
更新日期:2005-12-01 00:00:00
abstract:OBJECTIVE:There are limited data on cardiometabolic risk factors and the prevalence of metabolic syndrome (MetS) across the different PCOS phenotypes in Caucasian population. Lipid accumulation product (LAP) is a clinical surrogate marker that could be used for evaluation of MetS in clinical practice. The aim of the st...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-16-0775
更新日期:2016-12-01 00:00:00
abstract:OBJECTIVE:HRPT2 gene mutations are associated with parathyroid carcinomas, and absence of parafibromin immunoreactivity has been suggested as a diagnostic marker of malignancy. The aim of our study was to extend parafibromin studies in a series of benign and malignant parathyroid tumors and cross-validate the results o...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-06-0720
更新日期:2007-05-01 00:00:00
abstract:OBJECTIVE:Only a few studies have investigated variations of different markers for inflammatory processes during the physiological menstrual cycle. The results are conflicting, particularly concerning the correlation between the marker leptin and steroid hormones. The aim of the study was to investigate the inflammator...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.02178
更新日期:2006-07-01 00:00:00
abstract::Maintenance of fluid homeostasis during periods of heightened physical stress can be best evaluated in humans using exercise as a model. Although it is well established that arginine vasopressin (AVP), aldosterone and atrial natriuretic peptide (ANP) are the principle hormones regulating fluid balance at rest, the pot...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-08-0064
更新日期:2008-12-01 00:00:00
abstract:Objective:Children with Prader-Willi syndrome (PWS) have mild to moderate cognitive impairment. Short-term studies showed positive effects of growth hormone (GH) on cognitive development. This study investigated the effects of 8 years of GH on cognitive development in children with PWS. We also investigated whether sta...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-19-0479
更新日期:2020-04-01 00:00:00
abstract::Growth hormone (GH) is used by athletes like bodybuilders to increase muscle strength and weight gain. On the other hand, chronic hypersecretion of GH in active acromegaly may result in outwardly hypertrophied but functionally weaker muscles. As a model for studying long-term effects of GH on muscle strength, we analy...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1330735
更新日期:1995-12-01 00:00:00
abstract:OBJECTIVE:Glucocorticoids stimulate several steps in red blood cell (RBC) development; however, little is known on changes in erythroid parameters in patients with Cushing's disease. The aim of this study was to assess both RBC and white blood cell (WBC) parameters in a large cohort of patients with Cushing's disease a...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-13-0824
更新日期:2014-02-04 00:00:00
abstract:Aim:To establish pancreatic alpha-cell mass in lean, non-diabetic humans over the adult lifespan, performed as a follow-up study to beta-cell mass across the adult human lifespan. Methods:We examined human pancreatic autopsy tissue from 66 lean, non-diabetic individuals aged from 30 to 102 years, grouped into deciles:...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-19-0844
更新日期:2020-02-01 00:00:00
abstract:OBJECTIVE:To assess the LH response of the pituitary gland to GnRH stimulation in healthy women with a mutant beta-subunit (Trp8 to Arg8 and Ile15 to Thr15). DESIGN:Clinical study. PATIENTS:We studied 40 healthy non-pregnant Japanese women of known zygosity for the LH beta-subunit gene (3 homozygotes for the mutant g...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
doi:10.1530/eje.0.1430375
更新日期:2000-09-01 00:00:00
abstract:OBJECTIVE:According to the 2015 American Thyroid Association (ATA) guidelines, thyroid ablation by iodine-131 (I-131) therapy is absolutely recommended only in patients with high-risk differentiated thyroid cancer (DTC). Often distant metastases are not recognized early and they can stay silent for long time. The aim o...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-18-0253
更新日期:2018-09-01 00:00:00
abstract:OBJECTIVE:Slow-release (SR) lanreotide is a long-acting somatostatin analog that has been developed in order to overcome the inconvenience of multiple daily subcutaneous injections of octreotide, required for metabolic control in acromegaly. Lanreotide SR has been found to be well tolerated and effective in reducing GH...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1530/eje.0.1430577
更新日期:2000-11-01 00:00:00
abstract:OBJECTIVE:Polycystic ovarian syndrome (PCOS) is associated with skeletal muscle insulin resistance (IR), which has been linked to decreased mitochondrial function. We measured mitochondrial respiration in lean and obese women with and without PCOS using high-resolution respirometry. METHODS:Hyperinsulinemic-euglycemic...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-11-0419
更新日期:2011-10-01 00:00:00
abstract:OBJECTIVES:The purpose of this population-based prospective cohort study was to examine the effect of hormone therapy (HT) on incidence of diabetes mellitus (DM). DESIGN AND METHODS:Eight thousand four hundred and eighty-three DM-free post-menopausal women aged 52-62 from the population-based Kuopio osteoporosis risk ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0151
更新日期:2009-06-01 00:00:00
abstract:UNLABELLED:Chronic exposure to hypercortisolism has significant impact on patient's health and health-related quality of life (HRQoL), as demonstrated with generic questionnaires. We have developed a disease-generated questionnaire to evaluate HRQoL in patients with Cushing's syndrome (CS; CushingQoL). OBJECTIVE:Valid...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-07-0762
更新日期:2008-05-01 00:00:00
abstract:Objectives:Adipose tissue (AT) density measurement may provide information about AT quality among people living with HIV. We assessed AT density and evaluated relationships between AT density and immunometabolic biomarker concentrations in men with HIV. Design:Cross-sectional analysis of men enrolled in the Multicente...
journal_title:European journal of endocrinology
pub_type: 杂志文章,多中心研究
doi:10.1530/EJE-19-0296
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND:Identification of pretreatment risk factors predicting relapse in patients with hyperthyroidism of Graves' disease after stopping anti-thyroid drugs (ATD) is decisive to guide therapeutic options. PURPOSE:We performed a systematic search and meta-analysis to study predictors for relapse after stopping ATD i...
journal_title:European journal of endocrinology
pub_type: 杂志文章,meta分析,评审
doi:10.1530/EJE-16-0725
更新日期:2017-01-01 00:00:00