Endocrine Abstracts

Kallmann’s syndrome (KS) is proposed to result from disrupted migration of both olfactory sensory axons and hypothalamic gonadotrophin-releasing hormone (GnRH1) neurons during embryogenesis. KAL1 (encoding anosmin-1) and KAL2 (encoding the fibroblast growth factor receptor 1, FGFR1) are responsible for approximately 20% of KS cases, and in an ex vivo system it has been reported that anosmin-1 enhances FGFR1 signalling in a ligand (FGF)- and heparan su...

Introduction: Fructose-1,6-bisphosphatase (FBPase) deficiency is an autosomal recessive disorder causing failure of gluconeogenesis. Multiple mutations may produce the disease, of which 960/961insG is the commonest and is pan-ethnic. Hypoglycaemia, ketosis and lactic acidosis associated with the condition are triggered by infection, fasting or fructose/sucrose/sorbitol intake.Aim: To present an atypical case of FBPase deficiency and to demonstrate findin...

Introduction: Autosomal dominant Kallmann’s syndrome (AKS) results from mutations within the fibroblast growth factor receptor 1 (FGFR1: KAL-2). The FGFR family of tyrosine kinases are involved in a multitude of biological processes from embryogenesis to adult homeostasis. The crystal structure of FGF-FGFR-heparan sulphate (HS) ternary complex has provided a basis for understanding the way in which FGF, FGFR and HS cooperate to assist FGFR dimerization. Anosmin-1, KAL-1 g...

Understanding the molecular factors that regulate human muscle mass is acquiring increasing scientific interest. Hitherto, known (+ve) endocrine regulators of lean body mass included the GH-IGF-1 system, anabolic steroids, and (−ve) myostatin. In order to elucidate this process further, we have investigated a clinical case at a genetic and phenotypic level. A 46-year-old man with idiopathic muscle hypertrophy requiring multiple therapeutic fasciotomies underwent clinical...

During early embryogenesis, the olfactory axons and gonadotrophin-releasing hormone(GnRH)-secreting neurons undergo dynamic processes of differentiation, migration and proliferation, regulated by a complex network of molecular and cellular mechanisms responding to various hormonal and developmental signals. Mutations in anosmin-1 and FGFR1 disrupt this pathway, causing Kallmann's syndrome(KS), a human hereditary disorder with GnRH deficiency and inability to smell. A primary n...

GPR54 is a G protein coupled receptor identified in 2001 as the target for kisspeptin, the product of the KiSS-1 gene. Mutations in both kisspeptin and GPR54 lead to inherited failure to enter puberty (idiopathic hypogonadotropic hypogonadism) in the human, and a mutant mouse line with a targeted disruption of the Gpr54 receptor (Gpr54 -/-) has shown the same phenotype.Puberty begins when neurons in the hypothalamus begin pulsatile secretion of Gn...

GnRH is essential on reproductive physiology and behaviour. Early in development, GnRH-1 neurons undergo a migratory process from the olfactory placode (OP) to the hypothalamus. Failure of GnRH-1 migration and abnormal olfactory bulb (OB) characterize Kallmann's syndrome (KS) resulting in hypogonadotrophic hypogonadism and anosmia. The X-linked form of KS is due to a dysfunctional KAL-1 gene, which encodes anosmin-1. An autosomal dominant form of KS results from disrupted K...

Large databases facilitate the examination of those factors, which may determine response to treatment, potentially to develop prediction models. We have used KIMS (Pfizer's international metabolic database of GH-treated adults), to examine parameters that might predict clinical response to GH therapy in hypopituitary adults.Patients/methods: Patients with non-functioning pituitary adenoma on GH titrated to maintain serum IGF-I between minus 2 and 2 SDS,...

(This poster is based on OC11)...

Ghrelin is a 28 amino acid n-octanoylated peptide which is the natural agonist for the growth hormone secretagogue receptor and which potently stimulates GH release in vivo (1). We studied the effects of a somatostatin infusion on Ghrelin release in normal subjects.STUDY PROTOCOLFour females and five males, 25-40 years of age, body mass index < 28 kg per m2 were studied. Local ethics committee permission was obtained for ...