Abstract:
OBJECTIVE:Identification and characterization of calcium-sensing receptor (CASR) mutations in four unrelated Italian kindreds with familial hypocalciuric hypercalcemia. DESIGN:Clinical evaluation and genetic analysis of CASR gene. Functional characterization of mutated CASRs. METHODS:Direct sequencing of CASR gene in genomic DNA. Studies of CASR-mediated increases in cytosolic calcium concentration [Ca(2)(+)](i) in CASR-transfected COS-7 cells in vitro. RESULTS:Four unreported heterozygous CASR mutations were identified, including three missense (H595Y, P748H, and C765W) and one splice site (IVS2+1G>C) mutation. The H595Y, P748H, and C765W mutant receptors, although expressed at normal levels on the cell surface, showed a reduced response in [Ca(2)(+)](i) relative to the wildtype (WT) CASR to increasing extracellular calcium concentrations. Cotransfection experiments showed that the H595Y and P748H mutants did not affect the apparent affinity of the WT CASR for calcium, suggesting that they do not exert a dominant-negative effect. On the other hand, the co-transfected C765W mutant decreased the maximum response of the WT CASR to calcium, suggesting that it may reduce the effective concentration of the normal CASR on the cell surface or impair its maximal signaling capacity. CONCLUSIONS:Four CASR mutations were identified. The reduced functional responses to extracellular calcium and normal expression of the mutant receptors suggest that conformational changes account for altered CASR activity. Moreover, a reduced complement of normal CASRs in these heterozygous patients, perhaps combined with a mutant receptor-induced decrease in maximal activity of the WT receptor, may contribute to defective calcium-sensing in vivo.
journal_name
Eur J Endocrinoljournal_title
European journal of endocrinologyauthors
Cetani F,Lemmi M,Cervia D,Borsari S,Cianferotti L,Pardi E,Ambrogini E,Banti C,Brown EM,Bagnoli P,Pinchera A,Marcocci Cdoi
10.1530/EJE-08-0798subject
Has Abstractpub_date
2009-03-01 00:00:00pages
481-9issue
3eissn
0804-4643issn
1479-683Xpii
EJE-08-0798journal_volume
160pub_type
杂志文章abstract:BACKGROUND:Epidemiological studies suggest that hypopituitary patients have an increased risk for cardiovascular mortality. The dyslipidaemia associated with this condition is often characterised by an increase in total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol (LDL-C) and may contribute to these f...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.02105
更新日期:2006-03-01 00:00:00
abstract:OBJECTIVE:A sex difference in fetal and neonatal pituitary-gonadal function has been well documented. The aim of the following study was to determine sex differences and patterns of basal LH/FSH in the neonatal period. DESIGN:Peripheral venous blood was obtained from 164 healthy full term newborns (91 males, 73 female...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1430213
更新日期:2000-08-01 00:00:00
abstract:OBJECTIVE:Thyroid dysfunction predicts poorer health outcomes, but the relationship between thyroid hormone levels within the reference range and mortality in older adults remains unclear. In this study, we examined the associations between the concentrations of free thyroxine (FT4) and TSH and all-cause mortality in o...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-13-0306
更新日期:2013-09-12 00:00:00
abstract::Ionomycin, which mobilizes Ca2+, and phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), were used to compare the effects/interactions of Ca2+ and PKC on luteinizing hormone (LH) secretion from pituitaries of intact male and acutely ovariectomized (72 h) rats. Quartered pituitaries from dono...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1300151
更新日期:1994-02-01 00:00:00
abstract::The mineralocorticoid receptor (MR), a member of the steroid receptor family, acts as a transcription factor and mediates both aldosterone and cortisol effects. Aldosterone specificity in some tissues results from the inactivation of competing cortisol into cortisone by 11beta-hydroxysteroid dehydrogenase. In other ti...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1380702
更新日期:1998-06-01 00:00:00
abstract:Objective:Glucocorticoid treatment of inflammatory disorders is associated with significant adverse effects related to glucocorticoid excess as well as adrenal insufficiency. This necessitates awareness of its use. We therefore investigated trends in systemic glucocorticoid use as well as morbidity and comedications am...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-19-0305
更新日期:2019-09-01 00:00:00
abstract:OBJECTIVE:To i) compare incretin responses to oral glucose and mixed meal of diabetic patients with the normoglycaemic population and ii) to investigate whether incretin responses are associated with hypertriglyceridaemia and alanine aminotransferase (ALT) as liver fat marker. DESIGN:A population-based study. METHODS...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-13-0487
更新日期:2013-09-12 00:00:00
abstract:BACKGROUND:Mortality in acromegaly strictly depends on optimal control of GH and IGF1 levels. Modern medical therapy with somatostatin analogs (SSAs) and GH receptor antagonists (GHRAs) is not available in many countries due to funding restrictions. This retrospective, comparative, cohort study investigated the impact ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-13-1022
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND:Survival rates among childhood cancer survivors (CCS) have enormously increased in the last 40 years. However, this improvement has been achieved at the expense of serious late effects that frequently involve the endocrine system. AIM:To evaluate the cumulative incidence of endocrine diseases in a cohort of...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-12-1043
更新日期:2013-02-20 00:00:00
abstract::Bone loss due to menopause, natural or artificial, has been attributed solely to low estrogen. However, in a woman's life, the most precipitous bone loss begins 2 years prior to the last menstrual period, during which time estrogen levels are unperturbed whereas FSH is elevated. Our cell-based and mouse genetic studie...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-10-0397
更新日期:2010-07-01 00:00:00
abstract::The ob protein, termed leptin, is produced by adipocytes and is thought to act as an afferent satiety signal regulating weight through suppressing appetite and stimulating energy expenditure in humans and/or rodents. Insulin has been found to be a potent stimulator of leptin expression in rodents. It is unclear at pre...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1380501
更新日期:1998-05-01 00:00:00
abstract:BACKGROUND:17α-Hydroxylase/17,20-lyase deficiency (17OHD) caused by a mutation in the CYP17A1 gene is characterized by hypertension, hypokalemia, and abnormal development of the genitalia. The majority of CYP17A1 mutations are located in the coding sequence, and several intronic splicing site mutations have been report...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-10-0933
更新日期:2011-04-01 00:00:00
abstract::Glucocorticoid treatment causes osteoporosis and growth retardation in humans. Insulin-like growth factor I (IGF-I) stimulates differentiation and replication of cultured osteoblast-like cells and induces longitudinal bone growth in IGF-I-deficient rats. We investigated the influence of subcutaneously infused IGF-I on...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1300387
更新日期:1994-04-01 00:00:00
abstract:OBJECTIVE:Amine precursor uptake and decarboxylation is a classical feature of gastroenteropancreatic (GEP) neuroendocrine tumors (NET). Production of catecholamines was studied in GEP NET and non-NET patients. DESIGN:A cross-sectional study was undertaken. METHODS:We studied catecholamine and metabolite secretion in...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
doi:10.1530/eje.0.1400434
更新日期:1999-05-01 00:00:00
abstract:CONTEXT:Adult growth hormone (GH) deficiency (GHD) is diagnosed by provocative testing of GH secretion. OBJECTIVE:To improve the diagnostic accuracy of GH-releasing hormone (GHRH) plus arginine (GARG) testing, we evaluated the influence of age, BMI and sex and established normative data for an automatic immunoassay sp...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-16-0668
更新日期:2017-03-01 00:00:00
abstract::This study was designed to ascertain the long-term safety and efficacy profile of the somatostatin analogue octreotide as treatment of refractory acromegaly. Eight patients (aged 21-62 years) with persistent growth hormone (GH) elevation (duration 1-15 years) despite previous therapy were studied. Octreotide was given...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
doi:10.1530/eje.0.1320429
更新日期:1995-04-01 00:00:00
abstract:OBJECTIVE:Untreated hypothyroidism is common in iodine-replete areas. Frequent thyroid function testing and use of levothyroxine treatment for subclinical hypothyroidism suggest that the prevalence may have decreased. Therefore, in this study, we examined changes in the prevalence of hypothyroidism in a Norwegian count...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-13-0459
更新日期:2013-10-01 00:00:00
abstract:OBJECTIVE:The current guidelines for the management of adrenal incidentaloma advise hormonal and radiological follow-up of patients for 2-5 years after the initial diagnosis. However, the vast majority of adrenal incidentaloma are non-functional benign cortical adenomas that require no treatment, so the routine applica...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-15-0199
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Primary hyperparathyroidism (PHPT) is associated with increased cardiovascular mortality and morbidity. Little is known about hemostatic features of patients with PHPT. To our knowledge, plasma tissue factor pathway inhibitor (TFPI) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0069
更新日期:2009-05-01 00:00:00
abstract:OBJECTIVE:In female adrenal insufficiency, dehydroepiandrosterone (DHEA) secretion is impaired and circulating androgen levels are severely reduced. We wanted to analyse the acute effects of physiological DHEA substitution on substrate metabolism. DESIGN:We studied nine females with adrenal insufficiency after 9 days ...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1530/eje.1.01810
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Ki-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome maintena...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-15-0586
更新日期:2016-03-01 00:00:00
abstract:OBJECTIVE:The aim of the study was to evaluate the effect of intraoperative high-field (1.5 Tesla) magnetic resonance imaging (MRI) on the results of transsphenoidal surgery of GH-secreting pituitary macroadenomas. METHODS:Twenty-three acromegalic patients (mean tumor size, 25 +/- 12 mm; untreated preoperative GH, 4.2...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
doi:10.1530/eje.1.01970
更新日期:2005-08-01 00:00:00
abstract::Pyridostigmine (PST), a cholinesterase inhibitor, induces a clear growth hormone (GH) release in man by suppression of hypothalamic somatostatin (SRIH). Somatostatin suppresses thyrotrophin (TSH) release in rats and men. Earlier studies showed that the thryotrophin-releasing hormone (TRH)-induced TSH response was not ...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1530/eje.0.1330457
更新日期:1995-10-01 00:00:00
abstract:OBJECTIVE:Vitamin D insufficiency is common in primary hyperparathyroidism (pHPT). Patients with pHPT frequently have a reduced health-related quality of life (HRQoL). Our objectives were to evaluate whether HRQoL in pHPT is associated with vitamin D insufficiency and whether vitamin D supplementation after parathyroid...
journal_title:European journal of endocrinology
pub_type: 杂志文章,随机对照试验
doi:10.1530/EJE-14-0757
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:Glucocorticoids are the mainstay of immunosuppression for active moderate-severe Graves' orbitopathy (GO). AIM:To analyze the response to therapy and the contribution of glucocorticoid receptor (GR) gene polymorphisms to the therapeutic outcome of intravenous glucocorticoids (IVGC) in active moderate-severe...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-13-0611
更新日期:2013-11-22 00:00:00
abstract::Serum thyrotropin (TSH) concentration circadian rhythm is abolished in many endocrine and non-endocrine diseases. In the present study we have measured serum TSH concentration over 24 h every 2 h in second and third trimester pregnant women. During the 24-h period, serum free thyroxine and free triiodothyronine concen...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1330071
更新日期:1995-07-01 00:00:00
abstract:OBJECTIVE:To determine if functional imaging using 11C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment. DESIGN/METHOD...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-16-0639
更新日期:2016-11-01 00:00:00
abstract:OBJECTIVE:C-peptide, a cleavage product of insulin, exerts biological effects in patients with type 1 diabetes mellitus, but its role in type 2 diabetes mellitus is controversial. Our aim was to examine the associations between fasting C-peptide levels and all-cause mortality, specific-cause mortality and the incidence...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-12-0085
更新日期:2012-08-01 00:00:00
abstract::A 27-year-old woman with no previous personal or family history of thyroid disease was referred to us for the evaluation of thyroid nodule, five months postpartum. Thyroid scintigraphy demonstrated a left cold nodule. Fine needle aspiration cytology of the nodule showed a mixture of colloid, follicular cells and lymph...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1380562
更新日期:1998-05-01 00:00:00
abstract::The identification and sequencing of the ob gene and its product, leptin, in 1994 opened new insights in the study of the mechanisms controlling body weight and led to a surge of research activity. Since its discovery, leptin has been the subject of an enormous amount of work especially within the fields of nutrition,...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/eje.0.1490257
更新日期:2003-10-01 00:00:00