Endocrine Abstracts

Patient in the case, an 18-year-old male, complained of constant tiredness, frequent malaise, day time sleepiness, epigastric pain, poor appetite and consumption of great quantity of water. These conditions had persisted for 3–4 years. He had gone to many different physicians, with different tests taken, but without diagnose. Upon physical examination, the pale skin, scanty of pubic hair, and no presence of beard and axillary hair raised the possibility of Panhypopituitar...

Anosmin-1, a protein defective in X-linked Kallmann's syndrome (X-KS), presents a structure comprising a cysteine rich N terminus (CR), a whey acid protein (WAP) domain followed by four fibronectin-like III domains (FnIII); and its function is heparan sulphate (HS) dependent. However, anosmin-1 and HS binding affinity is unknown. Although the WAP domain belongs to a protein family demonstrating serine protease inhibitory activity, the interacting serine protease remains to be ...

Introduction: Anosmin-1, which is implicated in the pathogenesis of X-linked Kallmann`s syndrome, consists of a cysteine rich region, followed by a WAP domain and 4 fibronectin type III (FN3) domains. The N-terminal region of anosmin-1, WAP and 1st FN3 domain, is highly conserved in a wide variety of species which suggests that the activity of the protein resides in these conserved segments. Difficulties in the expression of the full-length anosmin-1 by Chinese hamster ovary c...

The defining features of Kallmann's syndrome (KS) are isolated hypogonadotrophic hypogonadism (IHH) and anosmia, the consequences of a GnRH neuronal migratory defect and olfactory bulb agenesis respectively. Additional features in X-linked Kallmann's syndrome (XKI), include unilateral renal agenesis and bimanual synkinesis respectively. XKI results from mutations of KALIG 1, on Xp22.3. The encoded protein anosmin-1, is a hexamodular secreted cell membrane associated extracellu...

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...

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...

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...

(This poster is based on OC11)...