报告题目：Mapping neuronal inputs to Kiss1 neurons in the mouse hypothalamus
报告人： William Colledge, Ph.D
Joint Head and Professor
Department of Physiology, Development and Neuroscience
University of Cambridge
时 间： 2019年10月29日（星期二）上午10:30-11:10
Infertility affects around 10-14% of couples globally and can significantly impact on the quality of life and the mental health of the individuals involved. Kisspeptins, a set of overlapping neuropeptides encoded by the Kiss1 gene, were originally identified as having an anti-metastatic activity in several cancer cell lines. It is now known, however, that kisspeptin is a key regulator of the mammalian reproductive axis and is required to initiate puberty by stimulating the release of gonadotropin stimulating hormone (GnRH) from the hypothalamus. Mice and humans with mutations in the kisspeptin signalling pathway have hypogonadotropic hypogonadism and are infertile. In addition to its role in puberty, kisspeptins are also required for ovulation. Indeed, analogues of kisspeptin are now being used as a potentially safer hormone regime to induce ovulation in women as part of in vitro fertilization treatments. Kiss1 neurons are found in two main areas of the hypothalamus: the arcuate (ARC) region, which regulates basal GnRH pulsatility and the anteroventral periventricular (AVPV) region, which controls the preovulatory LH surge. Kiss1 neurons are capable of integrating a variety of physiological signals to modulate the reproductive axis depending upon nutrition and environmental inputs. For example, it is thought that increased adiposity in young children and the action of leptin on kisspeptin expression can contribute to premature puberty in obese children. To understand better how the reproductive axis is regulated by these factors we have been mapping the neuronal circuitry into Kiss1 neurons. Several of these neuronal connections have been implicated as physiologically relevant in regulating the reproductive axis such as from the suprachiasmatic nucleus to control circadian ovulation. Moreover, kisspeptins have also been implicated in actions outside the brain such as a role in glucose metabolism, placentation and pregnancy. Thus, a full understanding of the physiological actions of kisspeptins and how they are regulated is vital to improving human reproductive health.
Professor William Colledge is joint Head of Department and Professor of Reproductive Physiology in the Department of Physiology, Development and Neuroscience (PDN) at the University of Cambridge. He obtained his BSc from Imperial College, London and his PhD from the National Institute for Medical Research, London. After a post-doctoral position in Ottawa, Canada, he joined the laboratory of the Nobel Prize winner Prof Sir Martin Evans in Cambridge. He then worked in the Gurdon Institute before he was appointed as a University Lecturer in the Department of Physiology, which merged with the Anatomy Department to form PDN. Professor Colledge teaches reproductive physiology and endocrinology to Medical, Veterinary and Natural Science Students.
Prof Colledge is an expert in the manipulation of mouse embryonic stem cells and the generation of transgenic mice. He has published 185 peer-reviewed publications and his h-index is currently 55 (ISI Web of Science). During his career, he has generated several important transgenic mouse models of human disease including cystic fibrosis and cardiac arrhythmias. His work with cystic fibrosis lead to Phase I clinical trials in the UK to evaluate a gene therapy treatment. His current research is focussed on understanding the neuroendocrine regulation of mammalian reproduction. His laboratory has played a major role in understanding the molecular events in the brain that are required for puberty and fertility. He has acted as a scientific consultant for several pharmaceutical companies including Paradigm Therapeutics, Takeda, Medimmune and Alloy Therapeutics.