title: Kallmann syndrome: towards molecular pathogenesis.
abstract: Gonadotropin Releasing Hormone (GnRH) is a key regulator of reproduction and sexual behaviour. During the last decade, embryological studies have clarified the question of the early development of GnRH-synthesising neurones before the onset of neurosecretion. These studies have revealed the existence of a topographical link between GnRH-synthesising neurones and the embryonic olfactory system, thereby shedding new light on Kallmann syndrome, a developmental disease characterised by the association of hypogonadotropic hypogonadism and anosmia (or hyposmia). Although Kallmann syndrome was identified as an inherited disease in the forties, familial cases of the disease are infrequent. However, the identification, by positional cloning strategies, of the gene underlying the X-chromosome linked form of the disease (KAL-1) has opened the way to molecular pathophysiology. KAL-1 encodes an extracellular glycoprotein of compound modular structure. The protein, named anosmin-1, has been produced in a transfected mammalian cell line and purified. Polyclonal and monoclonal antibodies have been generated, which allowed us to study the distribution of the protein during the period of human organogenesis (4--10 embryonic weeks), by immunohistofluorescence. During this developmental period, anosmin-1 is a locally restricted component of various extracellular matrices (interstitial matrices and basement membranes). Later in embryonic life, KAL-1 expression apparently becomes restricted to definite neuronal populations. Based on the distribution of anosmin-1 in the early olfactory system, the pathogenesis of the olfactory loss and GnRH deficiency in X-linked Kallmann syndrome is discussed.
authors: Unité de Génétique des Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, 25, rue du Dr Roux, 75724 Paris Cedex 15, France. hardelin@pasteur.fr
authors: J P
authors: JP
authors: Hardelin
mesh_terms: D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D006801:Humans; D017436:Kallmann Syndrome / Q000235:genetics / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009832:Olfactory Nerve / Q000002:abnormalities / Q000196:embryology / Q000502:physiology*; D014960:X Chromosome / Q000235:genetics
chemical_list: C076266:ANOS1 protein, human; D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D007987:Gonadotropin-Releasing Hormone