The proposed U54 Center at the University of Virginia will have a major goal of promoting translational research leading to application of new basic findings to clinical application. The Center theme is "Clinical and Basic Studies in Polycystic Ovarian Syndrome (PCOS)". This topic is appropriate to the goals of the Cooperative Centers Program, in that present therapeutic approaches to the anovulation and metabolic abnormalities in the disorder are of limited efficacy, and importantly, the basic mechanisms underlying PCOS remain uncertain. Current hypotheses as to of the etiology of PCOS center on regulation of GnRH secretion and action, and/or disordered ovarian function, either primary in nature or consequent to abnormal stimulation by gonadotropins or co-gonadotropins such as insulin and IGF-1. The U54 Center proposes 1 clinical project, 1 clinical pilot project, and 2 related basic projects to investigate these areas. Project I addresses abnormalities (testosterone induced resistance to progesterone action) in the regulation of the GnRH pulse generator in normal and obese adolescent girls and is directly related to basic studies in Projects II, modulation of GnRH-Gonadotrope responses - steroid-metabolic interactions, and Project III on steroid-metabolic interactions in the control of GnRH neurons. The pilot project is a clinical project addressing factors determining obesity-associated hyperandrogenemia in peripubertal girls. The Center subprojects are supported by two Cores proposed to operate under an "open access" formula. Overall integration of the research will be performed by the Administration Core, and specific laboratory services will be available to U54 projects and to eligible funded RSB program relevant projects through the Ligand Assay and Analysis Core, the latter having been designated a national resource by the RSB. The proposed U54 Center will build on the productive collegial atmosphere of the existing U54 Center at the University of Virginia and allow clinical and basic investigation of factors in the etiology of a common disorder of women during the reproductive years. The linking of basic and clinical projects will allow rapid transfer of basic information to clinical application, with the overall goal of enhancing our abilities to predict the disorder in adolescents and to enhance therapeutic approaches to PCOS with a resultant improvement in health for some 6-8% of women in the U.S.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD028934-19
Application #
8240002
Study Section
Special Emphasis Panel (ZHD1-DSR-L (54))
Program Officer
De Paolo, Louis V
Project Start
1997-04-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
19
Fiscal Year
2012
Total Cost
$1,340,345
Indirect Cost
$455,629
Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Wang, Huizhen; Larson, Melissa; Jablonka-Shariff, Albina et al. (2014) Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice. Proc Natl Acad Sci U S A 111:5735-40
Torchen, Laura C; Fogel, Naomi R; Brickman, Wendy J et al. (2014) Persistent apparent pancreatic ?-cell defects in premenarchal PCOS relatives. J Clin Endocrinol Metab 99:3855-62
Liu, D M; Torchen, L C; Sung, Y et al. (2014) Evidence for gonadotrophin secretory and steroidogenic abnormalities in brothers of women with polycystic ovary syndrome. Hum Reprod 29:2764-72
Collins, Jessicah S; Beller, Jennifer P; Burt Solorzano, Christine et al. (2014) Blunted day-night changes in luteinizing hormone pulse frequency in girls with obesity: the potential role of hyperandrogenemia. J Clin Endocrinol Metab 99:2887-96
Roland, Alison V; Moenter, Suzanne M (2014) Reproductive neuroendocrine dysfunction in polycystic ovary syndrome: insight from animal models. Front Neuroendocrinol 35:494-511
McGee, W K; Bishop, C V; Pohl, C R et al. (2014) Effects of hyperandrogenemia and increased adiposity on reproductive and metabolic parameters in young adult female monkeys. Am J Physiol Endocrinol Metab 306:E1292-304
Pike, Jack W; McDowell, Erin; McCahan, Suzanne M et al. (2014) Identification of gene expression changes in postnatal rat foreskin after in utero anti-androgen exposure. Reprod Toxicol 47:42-50
Garcia, Thomas X; Costa, Guilherme M J; Fran├ža, Luiz R et al. (2014) Sub-acute intravenous administration of silver nanoparticles in male mice alters Leydig cell function and testosterone levels. Reprod Toxicol 45:59-70
Lu, Guanyi; Su, Gang; Zhao, Yunge et al. (2014) Dietary phytoestrogens inhibit experimental aneurysm formation in male mice. J Surg Res 188:326-38
Anderson, Amy D; Solorzano, Christine M Burt; McCartney, Christopher R (2014) Childhood obesity and its impact on the development of adolescent PCOS. Semin Reprod Med 32:202-13

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