World population continues to increase at a frightening rate, particularly in developing countries. At the 1990 fertility rate (approximately 4 children per woman world-wide) there would be over 75 billion people on earth in the year 2100, compared to 6 billion at the present time. Even at the very optimistic projection of 2.5 children per woman, global population will grow to 19 billion by the year 2100. In addition, approximately one-quarter of all pregnancies are unwanted, leading to millions of abortions (1.5 million surgical or medical abortions annually in the United States) and approximately 100,000 deaths worldwide per year of otherwise healthy young women due to the complications of abortion. It is well established that men will use contraceptives (approximately 30% of all contraception in the U.S. now is accomplished with male methods). Therefore, the development of new, effective, safe, reversible male contraceptives is an extremely important societal goal. The work proposed in this application is designed to increase our basic and clinical knowledge of reproductive processes in the male with particular relevance to contraception. We are committed to excellence across the spectrum of studies proposed, from basic molecular biology and biochemistry through human physiology with direct application to contraceptive development. We have four research projects: 1) hormonal contraceptive studies in men (Dr. W. Bremner, PI), 2) genetic studies of the control of spermatogenesis in mice (Dr. R. Braun, PL), 3) studies of the roles of phosphodiesterases and their inhibitors in the testis (Dr. J. Beavo, PL), and 4) the cell-specific patterns of gene expression and their control in the testis (Dr. M. Griswold, PL). We also propose a Program for Fellows and New Investigators in Male Contraception and an Administration Core Unit. Our proposal incorporates the talents of outstanding investigators of varied backgrounds and professional training into an interactive research program in reproductive biology. We have structured this Center to meld superb science with the practical goal of applying new basic knowledge as quickly as possible to studies in human beings. We hope that, in this way, our work will address critical needs of society.

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 #
5U54HD042454-04
Application #
6849242
Study Section
Special Emphasis Panel (ZHD1-DRG-D (11))
Program Officer
Blithe, Diana
Project Start
2002-09-11
Project End
2007-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
4
Fiscal Year
2005
Total Cost
$2,080,705
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Berkseth, Kathryn E; Rubinow, Katya B; Melhorn, Susan J et al. (2018) Hypothalamic Gliosis by MRI and Visceral Fat Mass Negatively Correlate with Plasma Testosterone Concentrations in Healthy Men. Obesity (Silver Spring) 26:1898-1904
Rubinow, Katya B; Houston, Barbara; Wang, Shari et al. (2018) Androgen receptor deficiency in monocytes/macrophages does not alter adiposity or glucose homeostasis in male mice. Asian J Androl 20:276-283
Chen, Yan; Zhu, Jin-Yi; Hong, Kwon Ho et al. (2018) Structural Basis of ALDH1A2 Inhibition by Irreversible and Reversible Small Molecule Inhibitors. ACS Chem Biol 13:582-590
Paik, Jisun; Treuting, Piper M; Haenisch, Michael et al. (2018) Can inhibition of retinoic acid biosynthesis function as a non-hormonal female contraceptive? Contraception :
Sharma, Manju; Braun, Robert E (2018) Cyclical expression of GDNF is required for spermatogonial stem cell homeostasis. Development 145:
Rubinow, Katya B; Vaisar, Tomas; Chao, Jing H et al. (2018) Sex steroids mediate discrete effects on HDL cholesterol efflux capacity and particle concentration in healthy men. J Clin Lipidol 12:1072-1082
Haenisch, Michael; Treuting, Piper M; Brabb, Thea et al. (2018) Pharmacological inhibition of ALDH1A enzymes suppresses weight gain in a mouse model of diet-induced obesity. Obes Res Clin Pract 12:93-101
Swerdloff, Ronald S; Dudley, Robert E; Page, Stephanie T et al. (2017) Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels. Endocr Rev 38:220-254
Ayoub, R; Page, S T; Swerdloff, R S et al. (2017) Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive. Andrology 5:278-285
Rubinow, Katya B; Chao, Jing H; Hagman, Derek et al. (2017) Circulating sex steroids coregulate adipose tissue immune cell populations in healthy men. Am J Physiol Endocrinol Metab 313:E528-E539

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