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The fertile brain With infertility becoming more prevalent in Western societies, a new HRCfunded programme at the University of Otago’s Centre for Neuroendocrinology is focusing on how the brain controls fertility. Professor Allan Herbison from the Department of Physiology, Associate Professor Dave Grattan and Dr Greg Anderson from the Department of Anatomy and Structural Biology are pooling their expertise to find answers to key questions. A recent Fertility New Zealand study found nearly 25 per cent of New Zealand women report they have been infertile - defined as having been unable to conceive after having tried for over a year. Although the brain clearly controls fertility, surprisingly little is known about how. Understanding that would allow new therapies to be designed. The Otago programme has two broad aspects to it: One is understanding the basic biomedical science, such as where are the neurons in the brain that control fertility and how they work. The other looks at how nutrition impacts on the reproductive system. “What we do know is that there is a small group of cells in the brain called gonadotrophin-releasing hormone (GnRH) neurons that are the main players in determining fertility,” says Professor Herbison. “These cells secrete GnRH in an episodic manner - so once every hour or so they secrete a burst of GnRH. That burst results in a cascade of events that ultimately end in the ovary receiving a bursting, or pulsatile, control signal.” This is critical because if the hormone release doesn't occur in pulses then the ovary shuts down, he says. “A major component of the programme is aimed at understanding how the GnRH neurons are able to fire off every hour or so and give a pulse.” Studies using newly-invented imaging and electrical recording techniques in transgenic mice are now able to investigate GnRH neurons in detail like never before. The introduction of various transgenic approaches by the group has put them in a world-leading position to answer the fundamental questions. “Whereas most neurons communicate with each other through chemical synapses, our latest work is suggesting that GnRH neurons are using a different form of communication that involves direct electrical coupling,” Professor Herbison explains. “This is a very exciting possibility as it suggests that GnRH neurons may have very special or unique properties that would allow the development of selective agents for controlling their activity.” Associate Professor Grattan and Dr Anderson are using the same transgenic methodologies for research on the mechanisms through which nutrition impacts upon the neural control of fertility. “It looks like it is a delicate balancing act,” says Associate Professor Grattan. “On one hand, a woman needs to have sufficient reserves to enable a pregnancy to occur successfully, but on the other, too much fat seems to reduce fertility. This issue is especially timely considering that we are in the midst of an obesity epidemic.” The key hormone appears to be leptin; a molecule made by fat cells and secreted into the blood to tell the brain about the nutritional status and food reserves of the body. “So we are very interested in finding out how leptin regulates the bursting activity of the GnRH neurons” says Dr Anderson. This research is funded by the Health Research Council of New Zealand. HRC82 2006 Level 3, 110 Stanley Street, Auckland PO Box 5541, Wellesley Street, Auckland, NZ Telephone 64 9 303 5200 Facsimile 64 9 377 9988 Website www.hrc.govt.nz Professor Allan Herbison Key words: - fertility, hormone neurons Key facts: - Nearly 25 per cent of NZ women report they have been infertile - It is predicted that by 2010 in the United Kingdom one in three couples will require medical attention to help conceive - A small group of cells called gonadotrophin-releasing hormone (GnRH) neurons are key to determining fertility. Aims of this research: - to better understand the neurons in the brain that control fertility - to investigate how nutrition impacts on the reproductive system.