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Planning Grant for Establishing
a team to Investigate:
PI: Stephen Winters Co-PIs:
Project Duration:
One Year (June 1, 2005 – May 31, 2006) Abstract The University of Louisville requests funds to establish a Collaborative Research Development Program (CRDP) to support the academic development of a team of basic and clinical scientists who together will investigate the Neuroendocrine and Testicular Mechanisms in Male Infertility. Approximately 5-10% of men experience a fertility disturbance. Male infertility is not well understood, and treatment outcomes, other than in vitro fertilization using intracytoplasmic sperm injection, are poor, such that collaborative activities to investigate the pathophysiology and treatment of the problem are essential. We propose four innovative research projects designed to advance understanding of male fertility and infertility. Project 1 will determine the impact of obesity in adolescence on adult testicular function. We hypothesize that obesity and insulin resistance attenuate gonadotropin secretion in adolescence and thereby limit Sertoli cell proliferation. Fewer germ cells in adulthood lead to subfertility. Project 2 seeks to explore the mechanism for Leydig cell dysfunction in infertile men. We will pursue the idea that inhibin from Sertoli cells of the seminiferous tubules modulates activin signaling in Leydig cells to regulate testosterone synthesis by affecting transcription of Steroid Acute Regulatory (StAR) protein and the steroidogenic enzymes. Project 3, LH Signaling and Sertoli Cell Maturation, will use a genetically engineered mouse lacking the luteinizing hormone (LH) receptor that results in testosterone deficiency to study how Leydig cells influence the development and function of Sertoli cells and spermatogenesis. Project 4 will utilize a novel, non-invasive procedure to manipulate the timing of pubertal onset in the male rat, and will evaluate specific hormonal signals that may initiate testicular development. Funds will be used by this multidisciplinary group to obtain additional data and refine their tentative specific aims for submission of an application to the NIH Specialized Cooperative Center Program in Reproductive Biology. An external advisory board will be assembled to provide advice and guidance to the investigative team, and to review the NIH research grant application. Visiting professors in the field of reproductive biology will be invited to the University of Louisville. Finally, a weekly journal club will promote the close interaction among the members of the research team, and will advance the learning of their fellows and students. The proposal development will include such activities as visits to program managers at NSF, NASA, DoD, and HS (specifically HSARPA) and to other similarly focused centers, an extensive workshop aimed at the development of a competitive center proposal, visits to the University of Kentucky by distinguished researchers in the field to give seminars, and an exhaustive survey of the competitive landscape. |
