Endocrine Abstracts

Objective: Insulin-like growth factor-II (IGF-II), a critical regulator of placental development, enhances proliferation and survival of human cytotrophoblasts by signalling through the IGF-1 receptor (IGF-1R). Excess IGF-II binds to IGF-2R, which mediates its transport to the lysosomes for degradation. Although considered to act solely as an IGF-II clearance receptor, IGF-2R has been implicated in mediating IGF-II-stimulated migration and invasion in trophoblast. We therefore...

Adipogenesis is induced when intracellular cAMP increases and follows cell cycle arrest. During preadipocyte differentiation expression of the TSHR, which signals via cAMP and the inositol phosphate cascade, is upregulated. To investigate the role of TSHR activation in adipogenesis, we have developed an in vitro model in which constitutively active TSHR mutants (L629F, M453T) are introduced by retroviral vectors (RV).We aimed to compare the effect...

The TSHR is expressed during adipogenesis. We have employed in vitro models to investigate how TSHR activation affects this process. Gain-of-function TSHR mutants were introduced into preadipocytes using retroviral vectors. We have demonstrated that TSHR activation inhibits their proliferation and PPAR-gamma agonist (pioglitazone) induced adipogenesis. The aim of this study was to investigate the mechanisms operating.Non-modified primary human preadipocy...

In the adult animal the Leydig cells are the primary source of androgens in the male and are required to maintain fertility and male behaviour. To help towards understanding the development, control and function of these cells we have analysed the adult Leydig cell transcriptome using the SAGE technique which provides a comprehensive and quantitative gene expression profile of cells or tissues. Leydig cells were isolated from normal adult mouse testes using collagenase and the...

Pregnancy complicated by pre-existing or gestational diabetes is associated with increased risk of maternal and fetal mortality and morbidity. The most common complication, macrosomia, occurs during the third trimester of pregnancy as a result of abnormal placental growth and increased transfer of nutrients to the fetus. We have previously demonstrated using an explant model of human placenta, that statins have the potential to limit placental growth. In this study we tested t...

Objectives: Thyroid peroxidase (TPO) is a key enzyme in the synthesis of thyroid hormones and is a target for autoimmune responses in autoimmune thyroid disease. TPO autoantibody (TPOAb) binding epitopes have been mapped on the peroxidase domain (POD) and the complement control protein like domain (CCP). This study aimed to solve the molecular structures of TPO bound to TPO antibodies.Methods: An extracellular domain (ECD) of human TPO (amino acids; aa 1...

Introduction: Although oocyte donation (OD) is increasingly utilised in women with Turner’s syndrome (TS) few data are available. Reported clinical pregnancy rates following OD range from 17 to 40%. Complications of 2% death from aortic dissection and severe hypertension are reported.Aim: To analyse the OD-pregnancy success rate and materno-fetal outcomes in women followed in a TS-dedicated centre.Methods: A retrospective stud...

Aim: In diabetes, non-invasive lower-limb assessments including continuous wave Doppler (CWD), ankle-brachial index (ABI) and toe-brachial index (TBI) are recommended to assess vascular status due to increased risk of ulceration and amputation associated vascular pathology. How well these measurements can identify those at risk of these complications is unknown. The aim of this study was to investigate the relationship between a history of foot complication and non-invasive va...

Mutations in the leptin receptor gene (Lepr) occur spontaneously in humans and mice and are linked to early onset obesity and diabetes. Mice heterozygous for a signalling-deficient receptor (db/+) are widely used as a model of gestational diabetes that results in fetal macrosomia, but the contribution of the fetal genotype has yet to be evaluated. Eight week old wild type (wt) females (n=8) were mated to db/+ males and db/+ females (n=10) were mated to wt males i...

Introduction: The Autoimmune Polyendocrinopathy Syndromes (APS) comprise 4 clinical subtypes (1–4), APS type 1 is an autosomal recessive disorder caused by mutations in the AIRE (Autoimmune Regulator) gene. It should include at least 2 of the following 3 major criteria: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism (HPT) and adrenal insufficiency (AI) although 50% of patients develop all 3 features, usually before the age of 20 years. In addition, there are ...