Endocrine Abstracts

Introduction: In endocrine tumours, such as that of the breast, the protein survivin has emerged as a unique regulator of cell death. We have previously shown that bFGF regulates survivin expression through the MAP kinase cascade. The transcriptional complex myc/max is an oncogene that lies downstream of the MAP kinase pathway suggesting a possible role in survivin's regulation.Aim: To determine if bFGF can mediate survivin expression by signalling throu...

The kidney plays a dominant role in long-term blood pressure (BP) control and electrolyte homeostasis but aldosterone (aldo) responsive molecular pathways in the kidney involved in regulating BP remain poorly understood despite identification of several participant genes. Many human single gene disorders affecting BP have been faithfully reproduced in mice by targeting the corresponding genes. Thus mouse is an excellent model to study molecular pathways underlying hypertension...

Familial expansile osteolysis is a rare autosomal dominant disorder of bone, first described in a kindred from Northern Ireland in 1988. There are histological similarities to Paget's disease but the disorder typically presents in the young.Case report: Our patient presented at 15 years of age with sensorineural hearing loss, skeletal pain, gingival hypertrophy and mobile teeth. Neither parent was similarly affected. Radiographs demonstrated tooth root r...

Richard Eastell, Bone Metabolism Group, University of Sheffield, Sheffield, UK AbstractProfessor Eastell is Professor of Bone Metabolism at the University of Sheffield where he is also Director of Research for Medicine. He is the Research Dean for the School of Medicine and Biomedical Sciences, and Deputy Director of the Division of Clinical Sciences (North) at the University of Sheffield. He is also the Director for R...

Alpha melanocyte stimulating hormone (alpha-MSH) is an agonist at the melanocortin 3 receptor (MC3-R) and MC4-R and stimulates corticosterone release from rat and human adrenal cells. Patients with Cushing's syndrome have elevated levels of serum alpha-MSH. Agouti related protein (AgRP) is an endogenous antagonist at the MC3-R and MC4-R and is expressed in the rat adrenal cortex. AgRP antagonises alpha-MSH-induced corticosterone release from rat and bovine adrenal cells. This ...

Understanding human pancreatic beta cell differentiation provides safe, normal pathways by which to manipulate stem cells for the ambitious treatment of Type 1 diabetes (1-3). The transcription factor Neurogenin 3 (Ngn3) is a transient, yet critical regulator of this process, committing progenitor cells to an endocrine cell fate (4). However, the downstream consequences of NGN3 expression remain incompletely understood.To identify new target genes of NGN...

Glucocorticoid metabolism is altered in a tissue-specific manner in obesity. Increased reactivation of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) amplifies glucocorticoid action in abdominal fat, whereas increased metabolism of glucocorticoids by hepatic A-ring reductases may contribute to activation of the hypothalamic-pituitary-adrenal axis. These changes have been characterised in leptin-resistant obese Zucker rats and obese humans. Here we inves...

Aim: To investigate glucocorticoid (Gc) regulation of MIFBackground: MIF is a potent proinflammatory cytokine involved in inflammatory arthritis. Previous work suggested that MIF was induced by low concentrations of Gc, and may counteract their anti-inflammatory effect. The relationship between MIF and Gc has not been investigated in human cells.Methods: The human cell lines CEMC7A (T-lymphoblast) and A549 (lung epithelial) were us...

Intra-adipose steroid metabolism may be a key determinant of accumulation and distribution of body fat. Adverse 'central' fat can be driven by glucocorticoid excess or decreased oestrogen/androgen ratio. We previously demonstrated increased regeneration of cortisol by 11beta-HSD1 in adipose in human obesity. Here, we measured mRNAs for enzymes dictating local activation of oestrogens (aromatase) and androgens (5alpha-reductase type 1) in subcutaneous human adipose and related ...

The Northern Cancer Network Guidelines produced in 1999 for the management of differentiated thyroid cancer (DTC) state that patients should undergo two challenge scans after total thyroidectomy and radioiodine ablation; 6 months and 18 months after ablation. Due to the significant morbidity associated with thyroid hormone withdrawal in preparation for challenge scans, the need for the second scan has been questioned in the presence of a negative first scan and undetectable se...