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...

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: RAMPs (receptor activity-modifying proteins) are single-pass transmembrane accessory proteins required for appropriate signalling of the G-protein coupled receptors; CRLR (Calcitonin receptor like receptor) and CTR (Calcitonin receptor). There are three forms of human RAMPs known as, RAMP1, 2 and 3. RAMP3 heterodimerises with CRLR or CTR to form a high affinity receptor for the peptide hormones adrenomedullin and amylin, respectively. However, the exact mechanism...

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...

Background: The majority of patients with GH insensitivity have defects in the extracellular domain of the GHR. We have identified a 47yr old woman homozygous for a 22bp deletion in the cytoplasmic domain of the GHR. The patient had high GH levels, and low IGF-1 of 8 ug/L (normal 54-389 ug/L), IGFBP-3 16nmol/L (normal 61-254 nmol/L) and GHBP 6.8 percent (normal greater than 10 percent) levels. We report functional studies for this mutation (GHR1-449) which results in premature...

Background: Mutations in the GHR result in extreme short stature (Laron's syndrome). We have studied mutations from two patients with Laron's syndrome. Patient 1 (GHRextra) has a mutation in the GHR extracellullar domain due to a 108bp inframe pseudoexon between exons 6 and 7. Patient 2 (GHRintra) has a 22bp deletion in exon 10 of the GHR leading to premature termination of the GHR upstream of the intracellular STAT5 binding site.Aim: To compare GHR str...

Introduction: We have generated a truncated Growth Hormone Receptor (GHR) fused to the cell membrane by a glycosyl phosphatidylinositol anchor (GHR-GPI). The protein consists of the complete extracellular domain of the GHR, but lacks the intracellular domain, and we predict it would act as a GH antagonist. Aim: To test if partially-purified soluble GHR-GPI could re-insert into CHO cell membranes. Material and methods: Membrane preparations were made from CHO cells stably expre...

Seventeen newly-diagnosed acromegalic patients (8 female, 9 male: mean age 55 year, range 26–73 year) were recruited to the A.C.R.O.P.A.T. trial. Patients were assessed prior to, and following, 6 months of treatment with Somatuline Autogel® (SA).Growth hormone (GH) & insulin-like growth factor 1 (IGF1): Following treatment, GH and IGF1 levels fell significantly in all but one subject: median GH change −17.23 mU/l (interquar...