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Study identifies pathway required for normal reproductive development
Date:10/15/2007

Massachusetts General Hospital (MGH) clinical researchers, in collaboration with basic scientists from the University of California, Irvine (UC Irvine) have identified a new molecular pathway required for normal development of the reproductive, olfactory and circadian systems in both humans and mice. In their report to appear in the Proceedings of the National Academy of Sciences, the team describes defects in a gene called PROK2 (prokineticin 2) in human siblings with two different forms of infertility. The UC Irvine team had previously reported that mice lacking PROK2 had abnormal olfactory structures and disrupted circadian rhythm. The paper is receiving early online release.

We have demonstrated that PROK2 signaling is a novel pathway that is critical to the development of neurons that control the reproductive system, findings that should enable better understanding of human reproduction, says lead author Nelly Pitteloud, MD, of the Reproductive Endocrine Unit in the MGH Department of Medicine.

The current study is the latest in a series of investigations by the MGH group into the genetic basis of idiopathic hypogonadotropic hypogonadism (IHH), a rare condition in which puberty does not take place naturally. IHH occurs when a structure in the brain called the hypothalamus fails to develop neurons that secrete gonadotropin-releasing hormone (GnRH), a major controller of the reproductive system. Several genes involved in IHH have been discovered by the MGH investigators and others throughout the world; however, only 30 percent of IHH cases can currently be attributed to a known gene defect.

The investigation focused on PROK2, a protein known to regulate the development of the olfactory bulbs, the portion of the brain involved in the sense of smell, and to have a critical role in circadian rhythm in the mice. . A form of IHH called Kallmann syndrome involves lack of both reproductive development and a sense of smell. PROK2s
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

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