Endocrine Abstracts

Objectives: The homozygous GHR pseudoexon (6Ψ) mutation leads to aberrant splicing of the GHR gene with clinical and biochemical heterogeneity. We investigated whether the phenotypic variability could be explained by transcript heterogeneity i.e. ratio of abnormal (6Ψ GHR) to normal (WT GHR) transcripts and/or the presence of concurrent defects in other short stature (SS) genes.Methods: 6 Ψ GHR ...

A new genetic disorder has recently been identified that results from mutation of THRA, encoding thyroid hormone receptor α1 (TRα1). Affected children have a high serum T3:T4 ratio, constipation and a variable intellectual deficit, but exhibit a consistently severe skeletal dysplasia. Similar to these patients, Thra1PV/+ mice harbour a mutation that disrupts the C-terminal α-helix of TRα1 and express a domi...

Fluid restriction (FR) is the recommended first-line treatment for chronic hyponatraemia due to syndrome of inappropriate antidiuresis (SIAD) in expert guidelines, despite the lack of prospective data to support its efficacy. We aimed to test the hypothesis that FR was more effective than no treatment. 46 patients with chronic SIAD were randomised to either fluid restriction (1 litre/day, FR) or no specific hyponatraemia treatment (NoTx) for one month. Inclusion criteria were ...

Mice with dominant-negative mutations of thyroid hormone receptor α1 (TRα1) are euthyroid but display growth retardation and delayed bone age as juveniles and increased bone mass during adulthood, indicating impaired skeletal thyroid hormone responsiveness. The first autosomal dominant mutations affecting TRα1 in humans were recently described in two unrelated children and one parent who were euthyroid apart from a low T4:T3 ratio. Consiste...

T3-action is regulated by three iodothyronine deiodinases, which contain selenium in the active site. It is proposed that Se availability regulates thyroid function. OPUS is a European population-based prospective cohort study of post-menopausal women in which we showed thyroid function within the upper normal range is associated with reduced bone mineral density (BMD) and increased non-vertebral fracture risk. Using strict exclusion criteria we defined reference ranges for th...

Background: Guidelines on standards for diabetes care for children with type 1 diabetes (TID) recommend continuous (24 h/7-day-a-week) access to advice from specialist health-care professionals. However, for many diabetes teams, limited resources precludes provision of this service outside normal working hours. The use of regional networks may enable the implementation of safe, high quality and cost-effective support to patients and families ‘out of hours’.<p cla...

The Wellcome Trust Sanger Institute Gene Targeting Programme is deleting all mouse genes and has already generated 400 knockout mice in a C57/BL6N background with a further 4000 genes targeted in ES cells. Two hundred and fifty new knockouts will undergo limited phenotyping each year. However, the programme lacks a sensitive and sufficiently detailed screen for individual physiological systems, each of which requires high throughput methodology and unique expertise. Thus, we p...

Despite the recognized importance of thyroid hormones (TH) for normal brain development, little is known about the critical molecular events underlying this role. We investigated the molecular basis of TH action on the developing brain by: (1) comparing genome-wide gene expression patterns in the cerebellum of euthyroid, hypothyroid and hyperthyroid juvenile mice treated with 6-propyl thiouracil or mercapto-methylimidazole /perchlorate using DNA microarrays; and (2) investigat...

The hyperparathyroidism-jaw tumour (HPT-JT) syndrome, an autosomal dominant disorder, is characterised by the occurrence of parathyroid tumours, often carcinomas, and ossifying fibromata of the jaw. The HPT-JT gene, referred to as HRPT2, is located on chromosome 1q25 and consists of 17 exons that encode a 531 amino-acid protein designated parafibromin. To explore the role of HRPT2 in parathyroid tumourigenesis, we generated two mouse models that comprised a conve...

Current evidence suggests that the adipocyte-derived hormone resistin (RSTN) regulates both feeding and peripheral metabolism through unclear hypothalamic-mediated mechanisms. Here, we demonstrate by the first time, that the anorectic effect of RSTN is associated to specific changes in the expression of neuropeptides in the arcuate nucleus of the hypothalamus (ARC), namely AgRP, NPY and CART. Very interestingly, RSTN also exerts a deep, nutritional-dependent inhibitory effect ...