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Reduction of GnRH and infertility in the R6/2 mouse model of Huntington's disease.

Abstract
Reductions in testosterone and luteinizing hormone levels and reduced sexual functions have been reported in Huntington's disease (HD) patients. Atrophy of the reproductive organs and loss of fertility have also been observed in the R6/2 mouse, which is currently the most studied transgenic model of HD. In an effort to define the cause of infertility we studied the expression of gonadotropin-releasing hormone (GnRH) in the medial septum, diagonal band of Broca and hypothalamus of R6/2 male mice during sexual maturation. We found a progressive reduction in the numbers of GnRH-immunoreactive neurons in the analysed brain areas of R6/2 mice starting at 5 weeks of age and becoming statistically significant with only 10% of the neurons remaining by 9 weeks of age. Atrophy of testes and seminal vesicles combined with a significant reduction in serum and testicular testosterone levels were detected in 12-week-old R6/2mice. These results suggest that infertility in the R6/2 males is due either to death of GnRH neurons or to a reduction in GnRH expression leading to a downstream impairment of the gonadotropic hormones. Gonadotropic hormone replacement did not mitigate weight loss or restore motor function in R6/2 males.
AuthorsEugenia Papalexi, Anna Persson, Maria Björkqvist, Asa Petersén, Ben Woodman, Gillian P Bates, Frank Sundler, Hindrik Mulder, Patrik Brundin, Natalija Popovic
JournalThe European journal of neuroscience (Eur J Neurosci) Vol. 22 Issue 6 Pg. 1541-6 (Sep 2005) ISSN: 0953-816X [Print] France
PMID16190907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Serotonin Plasma Membrane Transport Proteins
  • Slc6a4 protein, mouse
  • Gonadotropin-Releasing Hormone
  • Testosterone
Topics
  • Algorithms
  • Animals
  • Body Weight (drug effects)
  • Brain Chemistry (genetics, physiology)
  • Disease Models, Animal
  • Gonadotropin-Releasing Hormone (metabolism)
  • Huntington Disease (genetics, metabolism)
  • Hypogonadism (genetics)
  • Immunohistochemistry
  • Infertility, Male (genetics)
  • Male
  • Mice
  • Mice, Transgenic
  • Organ Size (drug effects)
  • Serotonin Plasma Membrane Transport Proteins (genetics)
  • Testosterone (blood, pharmacology)

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