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Defective migration of neuroendocrine GnRH cells in human arrhinencephalic conditions.

Abstract
Patients with Kallmann syndrome (KS) have hypogonadotropic hypogonadism caused by a deficiency of gonadotropin-releasing hormone (GnRH) and a defective sense of smell related to olfactory bulb aplasia. Based on the findings in a fetus affected by the X chromosome–linked form of the disease, it has been suggested that hypogonadism in KS results from the failed embryonic migration of neuroendocrine GnRH1 cells from the nasal epithelium to the forebrain. We asked whether this singular observation might extend to other developmental disorders that also include arrhinencephaly. We therefore studied the location of GnRH1 cells in fetuses affected by different arrhinencephalic disorders, specifically X-linked KS, CHARGE syndrome, trisomy 13, and trisomy 18, using immunohistochemistry. Few or no neuroendocrine GnRH1 cells were detected in the preoptic and hypothalamic regions of all arrhinencephalic fetuses, whereas large numbers of these cells were present in control fetuses. In all arrhinencephalic fetuses, many GnRH1 cells were present in the frontonasal region, the first part of their migratory path, as were interrupted olfactory nerve fibers that formed bilateral neuromas. Our findings define a pathological sequence whereby a lack of migration of neuroendocrine GnRH cells stems from the primary embryonic failure of peripheral olfactory structures. This can occur either alone, as in isolated KS, or as part of a pleiotropic disease, such as CHARGE syndrome, trisomy 13, and trisomy 18.
AuthorsLuis Teixeira, Fabien Guimiot, Catherine Dodé, Catherine Fallet-Bianco, Robert P Millar, Anne-Lise Delezoide, Jean-Pierre Hardelin
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 120 Issue 10 Pg. 3668-72 (Oct 2010) ISSN: 1558-8238 [Electronic] United States
PMID20940512 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Gonadotropin-Releasing Hormone
Topics
  • Abnormalities, Multiple (pathology)
  • Cell Movement
  • Chromosomes, Human, Pair 13
  • Chromosomes, Human, Pair 18
  • Gonadotropin-Releasing Hormone (analysis)
  • Humans
  • Hypothalamus (pathology)
  • Kallmann Syndrome (pathology)
  • Neuroendocrine Cells (physiology)
  • Olfactory Bulb (abnormalities)
  • Preoptic Area (pathology)
  • Trisomy

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