Endocrine Abstracts

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 ...

Recent investigations into the pathogenesis of Kallmann's syndrome (KS) have pointed to the importance of anosmin-1 and FGFR1 (fibroblast growth factor receptor-1), the gene products for the X-linked and an autosomal dominant form of KS respectively, in olfactory, GnRH-1 neuronal systems and kidney ontogeny. Disturbed anosmin-1/FGFR1 pathways lead to partial or complete failure of OB (olfactory bulb) development and arrest of GnRH-1 neuronal migration, explaining the predomina...

IntroductionThe main population of GnRH-1 neurons that control activity of the HPG axis in primates originate in the peripheral olfactory system. Recently, in vitro primary cell cultures from human fetal olfactory epithelium, named FNC-B4, have been shown to express GnRH-1 and are likely to be the precursor of the adult-like GnRH-1 system distribution in the CNS. A number of external and cell-autonomous factors are known to control migration of these spe...

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...

(This poster is based on OC11)...