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Crucial sex hormones re-routed by missing molecule

29 November 2010

A hormone responsible for the onset of puberty can end up stuck in the wrong part of the body if the nerve pathways responsible for its transport to the brain fail to develop properly, according to research funded by the Biotechnology and Biological Sciences Research Council (BBSRC).

An optical section through a normal mouse nose showing the route the nerve cables (yellow) normally transport the GnRH through the nose (blue). The red shows the corridor inside the nose through which the nerve cables like to travel.

An optical section through a normal mouse nose showing the route the nerve cables (yellow) normally transport the GnRH through the nose (blue). The red shows the corridor inside the nose through which the nerve cables like to travel. Image: Dr Anna Cariboni

By tracking how nerve cells responsible for regulating sexual reproduction in mice find their way from their birth place in the foetal nose to their site of action in the adult brain, scientists from University College London (UCL) have found that if a certain molecule is missing, then these pathways are not formed correctly and gonadotropin releasing hormone (GnRH) can become lodged in the nose or the forehead, rather than in the brain, where it is needed to control the menstrual cycle in females and testosterone production in males.

Speaking about the findings, published today (29 November) in Human Molecular Genetics, co-investigator Dr Christiana Ruhrberg explains: "We discovered that a molecule essential for the growth of the nerve cables that transmit odour and pheromone signals from the nose to the brain is also crucial in the development of the highways responsible for transporting other nerve cells that make the sex hormone GnRH. We found that in mice with an inherited deficiency in the molecule SEMA3A, these highways did not lead to the brain, but instead formed impenetrable tangles outside the brain. This means that the nerve cells making GnRH are unable to get to their final destination and instead become stuck in the nose or forehead."

As a result the researchers found that the testes of mice lacking SEMA3A did not grow properly and the adult males were infertile. These findings have important implications for the study of Kallmann's syndrome and related genetic disorders that causes infertility.

Professor Douglas Kell, BBSRC Chief Executive said "This study highlights the importance of understanding the very earliest developmental processes of the brain, including how and where cells develop, how they migrate and how and where they mature. Such fundamental bioscience research helps drive medical advances by providing clues about the development of a variety of disorders which present huge challenges to individuals, their families and our wider society."

ENDS

Notes to editors

The paper can be downloaded from: http://hmg.oxfordjournals.org/content/early/2010/11/26/hmg.ddq468.full.pdf+html

The full paper is: Cariboni, A., Davidson, K., Rakic, S., Maggi, R., Parnavelas, J., Ruhrberg, C. (2010). Defective GnRH neuron migration in mice lacking SEMA3A signalling through NRP1 and NRP2: implications for the aetiology of hypogonadotropic hypogonadism. Human Molecular Genetics.

About UCL

Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. UCL is among the world's top universities, as reflected by performance in a range of international rankings and tables. Alumni include Marie Stopes, Jonathan Dimbleby, Lord Woolf, Alexander Graham Bell, and members of the band Coldplay. UCL currently has over 13,000 undergraduate and 9,000 postgraduate students. Its annual income is over £700M. www.ucl.ac.uk

About BBSRC

BBSRC is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £470M in a wide range of research that makes a significant contribution to the quality of life in the UK and beyond and supports a number of important industrial stakeholders, including the agriculture, food, chemical, healthcare and pharmaceutical sectors.

BBSRC provides institute strategic research grants to the following:

  • The Babraham Institute
  • Institute for Animal Health
  • Institute of Biological, Environmental and Rural Sciences (Aberystwyth University)
  • Institute of Food Research
  • John Innes Centre
  • The Genome Analysis Centre
  • The Roslin Institute (University of Edinburgh)
  • Rothamsted Research

The Institutes conduct long-term, mission-oriented research using specialist facilities. They have strong interactions with industry, Government departments and other end-users of their research.