Neuroendocrine control of the reproductive axis

Abstract

RESEARCH THEME: The scientific papers presented in this bound volume reflect 20 years' worth of research that I have performed since obtaining my M.Sc., from the University of Edinburgh. The primary focus of this research has been in the field of reproductive neuroendocrinology, where I have tried to integrate findings from different experimental animal models to help elucidate the neuroendocrine mechanisms that control reproductive function. Inevitably, this has also led me to examine related topics such as glutamatergic and GABA-ergic neurotransmitter systems, circadian neuroendocrine rhythms, and environmental-neuroendocrine interactions. It is hoped that these basic studies will provide new insights into the development of effective therapies for human reproductive disorders.RESEARCH HIGHLIGHTS: (1) Having established a novel remote blood sampling set-up, I was able to clearly demonstrate that sex-steroid-independent diurnal changes in the pulsatile pattern of luteinizing hormone (LH) secretion play a central role in triggering the onset of puberty in female rats; (2) I was subsequently able to show that glutamate receptors represent a fundamental component of the reproductive neuroendocrine axis, and that their manipulation can profoundly influence reproductive function; (3) By developing mouse monoclonal antibodies that are highly specific to gonadotrophin-releasing hormone (GnRH), I made it possible for GnRH-producing neurones to be chemically characterized using multiple-label immunohistochemistry; so far, I have freely distributed these antibodies to >70 investigators around the world; (4) Through a series of photoperiodic and histochemical studies I was able to establish that an area of the brain known as the bed nucleus of the stria terminalis represents a key relay station for environmental signals that impinge on the GnRH neuronal circuits of seasonal breeding species; this finding has also helped to establish the hamster as an experimental model for seasonal affective disorder, (5) Traditionally, the neurotransmitter GABA was thought to exert its influence on the reproductive axis exclusively by its actions at the level of the hypothalamus; but this idea has now been brought into question because of my novel finding that GABA is also highly expressed within the pituitary gland itself; (6) Traditionally, control of gonadotrophin secretion in mammals was thought to be controlled by a single neuropeptide, known as mammalian GnRH or GnRH-l; my recent cloning of a second form of the GnRH (GnRH-ll), and demonstration of its unique expression pattern in the rhesus monkey hypothalamus, has opened up a new way of thinking about how the hypothalamus controls reproductive function.SCIENTIFIC PUBLICATIONS: Altogether, this research has resulted in the publication of 110 abstracts, which were presented either at national or international scientific meetings. A complete list of these abstracts is included in this volume, the most notable being: (1) the keynote address "Seasonal Reproduction" at the Canada West Society for Reproductive Biology, (Edmonton, Canada, 1992) (2) presentation of the Walpole Memorial Lecture "N-methyl-Daspartate receptor gene expression in the hamster hypothalamus and in immortalized luteinizing hormone-releasing hormone neurones" at the annual meeting of the Society for the Study of Fertility (Cambridge, England, 1993); and (3) the invited symposium presentation "Development and Aging of the Neuroendocrine Reproductive Axis of the Rhesus Macaque" at the International Primate Symposium (Inuyama City, Japan, 2000). The research has also resulted in the publication of 70 peer-reviewed papers and book chapters, including "Puberty in the Rat" (In; Physiology of Reproduction. Raven Press) which is considered to be one of the most definitive reviews of sexual maturation in rodents, and "Influence of Light and the Pineal Gland on Biological Rhythms" (In: Neuroendocrinolqy in Physiology and Medicine. Humana Press) which is considered to be one of the most comprehensive texts on the subject written specifically for medical and graduate students. The bound volume contains a collated set of these published papers, together with copies of eleven journal covers which feature original artwork/figures from my research (Journal covers include: Brain Research, Developmental Brain Research, Endocrinology, Journal of Endocrinology, and Molecular Brain Research).GRANT SUPPORT: None of my research would have been possible without financial support, predominantly in the form of competitive grants from the National Institutes of Health. I am extremely grateful for this continued support, which currently exceeds $500,000 per year in direct costs. As a form of scientific reciprocation, I have reviewed numerous grants for various funding agencies during the past two decades, including the National Institutes of Health (NIH). National Science Foundation. Canadian Institutes of Health Research. Natural Sciences and Engineering Research Council of Canada, and Agricultural and Food Research Council of the United Kingdom. I have also been an acf doc reviewer of manuscripts for 20 different scientific journals, and I currently serve on the editorial board of the journal Endocrinology

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