Abstract:
:Several converging lines of evidence obtained over the last years in a wide variety of experimental model organisms suggest that the ageing process is regulated by genes that encode proteins from the somatotroph axis: longevity genes like daf-2, which were identified using mutant Caenorhabditis elegans strains, turned out to be orthologues of the mammalian genes encoding insulin-like signalling cascade proteins. Transgenic flies with mutations in the corresponding insect genes showed a similar pattern of increased lifespan. Finally, mice with spontaneous mutations leading to pituitary hormone deficiency significantly outlived controls. While these and other genetic models suggest that the downregulation of the somatotroph axis can slow the ageing process, other results from studies using pharmacological administration of growth hormone suggest that such stimulating treatment can restore some of the phenotypic traits associated with youth. To better understand the role of the insulin-like receptors in mammalian lifespan regulation and ageing, we explored the phenotype of heterozygous IGF-I receptor (IGF1R) knockout mice. Compared with control littermates these mutants live longer without any obvious impairment of their health and physiology, except a reduced glucose tolerance that we observed in males. These IGF1R(+/-) mutants were also more resistant to oxidative stress in vivo, and we identified a possible molecular pathway linking underphosphorylation of IGF-I receptors to the lack of activation of p66Shc, a protein capable of increasing resistance to oxidative stress through regulation of a set of downstream genes. These and other results suggest that in mammals too, lifespan can be increased by continuous, long-term downregulation of IGF signalling. Since growth hormone administration normally stimulates IGF production in tissues, the question arises whether the beneficial effects of GH, as reported by others, could be IGF independent. This hypothesis can be addressed, for example, by adequately combining existing transgenic mouse models.
journal_name
Eur J Endocrinoljournal_title
European journal of endocrinologyauthors
Holzenberger Mdoi
10.1530/eje.0.151s023subject
Has Abstractpub_date
2004-08-01 00:00:00pages
S23-7eissn
0804-4643issn
1479-683Xjournal_volume
151 Suppl 1pub_type
杂志文章abstract:BACKGROUND:Gastric carcinoid tumours type 1 (GCA1) originate from hyperplastic enterochromaffin-like (ECL) cells secondary to hypergastrinaemia. Treatment with somatostatin analogues (SSA) might impede ECL-cell hyperplasia by suppressing gastrin secretion and/or by a direct anti-proliferative effect on ECL cells. We co...
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-08-0420
更新日期:2008-10-01 00:00:00
abstract:OBJECTIVE:The intrarenal renin-angiotensin system (RAS) activation plays a pivotal role in immunoglobulin A nephropathy (IgAN) pathogenesis, which is still largely undefined. Recently, vasopressin (AVP) has been advocated to contribute to the genesis and progression of chronic kidney diseases (CKD) directly, and indire...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-11-0512
更新日期:2011-10-01 00:00:00
abstract::The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification c...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-15-0937
更新日期:2016-04-01 00:00:00
abstract:OBJECTIVES:Investigation of small numbers of parathyroid tumours by X-chromosome inactivation analysis suggests that the majority of them are monoclonal lesions most likely caused by a somatic mutation. Somatic mutations in the MEN1 gene located on chromosome 11q13 have recently been identified in 12-17% of solitary pa...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1430047
更新日期:2000-07-01 00:00:00
abstract::We examined excretion of urinary insulin-like growth factors I and II (IGF-I and IGF-II) and their major binding protein IGFBP-3 in comparison to their respective serum concentration in nine healthy female volunteers (median age 25 years, range 22-27) under baseline conditions and after stimulation with recombinant hu...
journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章
doi:10.1530/eje.0.1320433
更新日期:1995-04-01 00:00:00
abstract:BACKGROUND:The human androgen receptor (AR) gene contains two polymorphisms of CAG and GGN repeats respectively. The GGN repeat function is still largely unknown and to date there are no in vivo data on this segment with respect to the general population. METHODS:We investigated the impact of CAG and GGN repeats on ma...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.1.02204
更新日期:2006-08-01 00:00:00
abstract::The aim of this study was to investigate the frequencies of clinical diabetes and humoral markers of anti-pancreatic autoimmunity in a homogeneous population of 600 Caucasian patients with recently diagnosed Graves' disease (GD), in order to characterize the specific features of this group of endocrine patients among ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1370503
更新日期:1997-11-01 00:00:00
abstract:OBJECTIVE:To compare clinical and humoral parameters before and after surgery in patients with incidental adrenocortical adenomas. DESIGN:Six patients with subclinical Cushing's syndrome and nine with non-functioning adenomas were investigated before and 12 Months after removal of the mass. METHODS:Anthropometric (bo...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1480213
更新日期:2003-02-01 00:00:00
abstract:OBJECTIVE:Primary hyperparathyroidism (pHPT) is characterized by excessive production of parathyroid hormone (PTH) due to parathyroid adenomas while uremic secondary HPT (sHPT) is caused by parathyroid hyperplasia in response to renal failure. Active vitamin D, 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), with the vi...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1470671
更新日期:2002-11-01 00:00:00
abstract:Objective:To evaluate the prevalence and natural course of autoimmune and non-autoimmune subclinical hypothyroidism (SH) in Down syndrome (DS) children and adolescents. Design:Prospective multicenter study. Methods:For the study, 101 DS patients with SH (TSH 5-10 mIU/L; FT4 12-22 pmol/L), aged 2-17 years at SH diagno...
journal_title:European journal of endocrinology
pub_type: 杂志文章,多中心研究
doi:10.1530/EJE-19-0823
更新日期:2020-04-01 00:00:00
abstract::Over the last 5 years, new actors involved in the pathogenesis of combined pituitary hormone deficiency in humans have been reported: they included a member of the immunoglobulin superfamily glycoprotein and ciliary G protein-coupled receptors, as well as new transcription factors and signalling molecules. New modes o...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-15-1095
更新日期:2016-06-01 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:Thyroid hormone (TH) transporters are expressed in thyrocytes and most play a role in TH release. We asked whether expression of the monocarboxylate transporter 8 (MCT8) and the L-type amino acid transporters LAT2 and LAT4 is changed with thyrocyte dedifferentiation and in hyperfunctioning thyroid tissues. D...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-17-0279
更新日期:2017-09-01 00:00:00
abstract::Previous work has examined potential links between the etiology of GH deficiency (GHD) and the baseline characteristics of the patients including biochemical and psychometric parameters. Using an update of the KIMS pharmaco-epidemiological database (Pfizer International Metabolic Database), we addressed the question h...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0273
更新日期:2009-11-01 00:00:00
abstract:OBJECTIVE:Subclinical hypothyroidism occurs in a number of children with Down's syndrome (DS). The reason for the mildly elevated plasma thyrotropin (TSH) concentrations is not known. The present study investigated whether decreased TSH bioactivity plays a role in this phenomenon. DESIGN:A retrospective study of plasm...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1440001
更新日期:2001-01-01 00:00:00
abstract::Puberty is the result of increasing pulsatile secretion of the hypothalamic gonadotropin releasing hormone (GnRH), which stimulates the release of gonadotropins and in turn gonadal activity. In general in females, development of secondary sex characteristics due to the activity of the gonadal axis, i.e., the growth of...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-08-0314
更新日期:2008-12-01 00:00:00
abstract::Little is known about patients with malignant digestive neuroendocrine tumours (MD-NETs). Although their incidence is increasing, MD-NETs remain a rare cancer, representing 1% of digestive cancers. Most MD-NETs are well-differentiated. MD-NET poorly differentiated carcinomas account for 20% of cases on average. Anatom...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-12-0418
更新日期:2013-03-15 00:00:00
abstract::Vasoactive and angiogenic factors are involved in the autocrine/paracrine thyroid regulation of microvascular bed during goiter development. In the thyroid of old mice, the presence of slowly functioning ('cold') follicles allowed us to study the microvascular regulation of each follicle in correlation with the immuno...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1420651
更新日期:2000-06-01 00:00:00
abstract:Objectives:Male hypogonadism is associated with higher risk of co-morbidity and premature mortality. It is, therefore, of utmost importance to identify young men who are at the highest risk of testosterone deficiency and who may benefit from preventive measures. In this context, infertile men constitute a high-risk gro...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-19-0734
更新日期:2020-04-01 00:00:00
abstract:BACKGROUND:Somatostatin analogs (SA) are the cornerstone in the medical treatment of acromegaly, used as either primary or adjunctive therapy. In particular, SA are effective in inducing the biochemical remission of the disease and tumor shrinkage, although only few cases of complete disappearance of the pituitary tumo...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-09-0769
更新日期:2010-05-01 00:00:00
abstract:OBJECTIVE:In view of their different actions on thyroid hormone receptor (TR) isoforms we set out to investigate whether amiodarone (AM) and dronedarone (Dron) have different and/or component-specific effects on cardiac gene expression. DESIGN:Rats were treated with AM or Dron and the expression of TRalpha 1, TRalpha ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-07-0017
更新日期:2007-06-01 00:00:00
abstract:OBJECTIVE:To assess the value of the diagnostic whole body (131)I scan after thyroidectomy and (131)I ablation. DESIGN:Retrospective analysis of all patients with differentiated thyroid cancer treated in one centre between 1990 and 2000. RESULTS:A total of 153 consecutive patients who underwent diagnostic scanning fo...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1500649
更新日期:2004-05-01 00:00:00
abstract::We here investigate the potential rescue of the relative hyposomatotropism of aging and obesity by 3-day pulsatile GHRH infusions (i.v. bolus 0.33 microg/kg every 90 min) in 19 healthy men of varying ages (18 to 66 years) and body compositions (12 to 37% total body fat). Baseline (control) and GHRH-driven pulsatile GH...
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.0.1390059
更新日期:1998-07-01 00:00:00
abstract::Recombinant human GH has been licensed for use in adult patients with GH deficiency (GHD) for over 15 years. Early weight- and surface area-based dosing regimens were effective but resulted in supraphysiological levels of IGF1 and increased incidence of side effects. Current practice has moved towards individualised r...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-12-0563
更新日期:2013-02-20 00:00:00
abstract::We studied the roles played by the renin-angiotensin system in inducing hypertension in nine patients with Cushing's syndrome (CS) resulting from adrenocortical adenoma, and compared them with those in patients with primary aldosteronism (PA), renovascular hypertension (RVH) and essential hypertension (EH). In the CS ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1310582
更新日期:1994-12-01 00:00:00
abstract:OBJECTIVE:Late diagnosis hinders proper management of small intestine neuroendocrine carcinoma (SI-NEC) patients. The olfactory receptor, family 51, subfamily E, member 1 (OR51E1) has been reported as a potential novel SI-NEC marker, without protein expression recognition. Thus, we further studied whether the encoded p...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-12-0814
更新日期:2013-01-17 00:00:00
abstract::The p16INK4A and p15INK4B genes on chromosome 9p21 encode the p16 and p15 inhibitors of cyclin D/cyclin-dependent kinase 4 complexes respectively. Mutations and deletions of the p16INK4A gene have been found in melanomas and many other types of tumors. To assess the role of the p16INK4A and p15NK4B genes in tumorigene...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1360074
更新日期:1997-01-01 00:00:00
abstract:OBJECTIVE:The alpha(2)-adrenergic receptors are involved in the effects of catecholamines on energy metabolism. Of three known subtypes with differential expression, alpha(2A)-adrenergic receptors are also localized in adipose tissue where they counteract the lipolytic activity of beta-adrenergic receptors. This study ...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1440291
更新日期:2001-03-01 00:00:00
abstract:OBJECTIVES:The French Acromegaly Registry records data of acromegalic patients' since 1992 in French, Belgian (Liège), and Swiss (Lausanne) centers. We studied the prevalence of diabetes in this population looking for risk factors. Patients from one of the centers (Reims) were then analyzed more thoroughly. METHODS:Th...
journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-10-1050
更新日期:2011-06-01 00:00:00
abstract::Osteopetrosis is a rare metabolic bone disease characterized by a generalized increase in skeletal mass. It is inherited in a number of mammalian species, including man, and results from a congenital defect in the development or function of the osteoclasts. The consequent impairment of bone resorption prevents formati...
journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/eje.0.1340143
更新日期:1996-02-01 00:00:00