NSF Award
9308952
9308452 Demski Gonadotropin-releasing hormone (GnRH) is a decapeptide that was isolated from brain in 1971. This hormone is released from neurons of the anterior basal forebrain which project through the ventral hypothalamus to the median eminence and act upon the pituitary to regulate the control of luteinizing hormone and follicle stimulating hormones. Thus, GnRH plays a pivotal role in ovulation and testosterone production. However, with the development of sensitive and specific antibody techniques, it has now become clear that GnRH neuronal network is a complex, heterogenous system, comprising three or more discrete neuronal groups and spanning vastly different regions of the brain. Besides the hypothalamic area, the peptides are produced in cells in the terminal nerve ganglia and the midbrain tegmentum near the oculomotor complex. Little is known of the physiological roles that these two other neuronal systems may play. Using state-of- the-art neuroanatomical techniques, Dr. Demski and his undergraduate students will map the functional connections of GnRH system in these brain regions. They will provide a detailed anatomical examination of developing brains. A special retrograde neural tracer will be used to identify cellular connections between GnRH-containing neurons and cerebral blood vessels. In addition, Dr. Demski will lesion the terminal nerve at different stages of development and determine the effects on the physiology and development of specific behaviors. The results should provide new insights into the organization, function and mechanisms of action of the GnRH systems lying outside the endocrine hypothalamus. Moreover, many reproductive dysfunctions in humans result from a disorder in the GnRH system. For example, Kallman's Syndrome, a congenital disorder characterized by sterility and anosmia, is caused by a defect in the migration of GnRH neurons and hypogonadism, characterized by delayed puberty and sterility, results from Gn RH deficiency. Fundamental information gained from this work may help facilitate the development of effective treatments for patients suffering from GnRH dysfunctions. ***
