Endocrine Abstracts

INTRODUCTION: We have been interested to investigate the biological activity of mutant molecules of growth hormone. Purification of growth hormone requires multiple steps. We have investigated a method to purify growth hormone which would be applicable to most protein hormones that bind to cell surface receptors.AIM: To test whether his-tagged extracellular domain growth hormone receptor could be used to purify recombinant growth hormone.<p class="ab...

BackgroundPPAR-gamma agonists have been proposed as therapy to lower plasma ACTH in Cushing's disease. However, cyclical secretion may explain some of the 'responses' seen. In contrast, patients with Nelson's syndrome have continual high ACTH levels, and can present with pituitary mass effects and pigmentation. Since no established medical therapy exists, we assessed whether prolonged high-dose rosiglitazone therapy reduces circulating ACTH levels in Nel...

BackgroundPPAR-gamma agonists have been proposed as therapy to lower plasma ACTH in Cushing's disease. However, cyclical secretion may explain some of the 'responses' seen. In contrast, patients with Nelson's syndrome have continual high ACTH levels, and can present with pituitary mass effects and pigmentation. Since no established medical therapy exists, we assessed whether prolonged high-dose rosiglitazone therapy reduces circulating ACTH levels in Nel...

Pegvisomant is a specific GH antagonist developed for the treatment of acromegaly. Pegvisomant is a GH antagonist molecule with an amino acid substitution that blocks the conformational change necessary for signal transduction and polyethylene glycol (PEG) moieties to improve clinical efficacy. Pegvisomant has a long plasma half-life and its mode of clearance has not been established. We hypothesised that GHR mediated internalisation of Pegvisomant might be one mechanism for i...

Introduction: Leptin modulates immune activation in relation to nutritional state and there is gender difference in body composition and the immune response. Leptin induces the release of pro-inflammatory cytokines, including TNF-alpha, from human peripheral blood mononuclear cells (PBMCs). We hypothesised that estrogen may modulate the immune actions of leptin. Aim: To test the effect of estrogen on leptin signalling and leptin-induced TNF-alpha production. Materials and Meth...

Background: The introduction of somatostatin analogues for the treatment of acromegaly has relegated dopamine agonists, once a mainstay of treatment, down the therapeutic ladder. Dopamine agonists are, however, added to somatostatin analogues to control active disease in some patients, in an attempt to achieve biochemical control. There are no reports, however, assessing this practise.Aim: To assess the effectiveness of adding dopamine agonist therapy to...

Background: Leptin, the satiety hormone that is produced by adipose tissue appears to act as a link between nutritional status and immune function, and it has been shown to elicit a number of immunoregulatory effects, including the promotion of T cell proliferative responses, and the elicitation of pro-inflammatory cytokines from T cells and monocytes. Given that leptin deficiency is associated with an increased susceptibility to infection, and that polymorphonuclear neutrophi...

Objectives: To assess bone mineral density (BMD) and body composition in adults with congenital adrenal hyperplasia (CAH).Setting: Endocrine clinics in seventeen centres throughout the UK participating in CaHASE, a Society for Endocrinology project.Study design and subjects: Cross-sectional survey of 203 adults with CAH (65 men, 138 women: median age 33 (range 18–70) years). Hundred and sixty six patients were classified as cl...

Background: Leptin is an important regulator of the immune response. Therapeutics that modulate leptin signalling are considered to be a potential targets in a number of immune related conditions. The role of leptin antagonists to suppress the immune system, slowing the progression of autoimmune diseases is a widely discussed idea. However, leptin agonists may also be useful to up-regulate the immune response during malnutrition. The aim of this project was to develop long-las...

Introduction: The growth hormone receptor (GHR) consists of 620 residues and belongs to the class I cytokine receptor family. It is a single membrane spanning protein that binds its ligand, GH, via the extracellular domain. GH binding to GHR induces a conformational change in the preformed receptor dimer, which leads to intracellular signalling. Correct functional dimerisation of two GHR molecules is essential for GH signalling. We have previously shown that membrane bound tru...