Abnormalities of testicular decent represent some of the most common diagnoses in pediatric urology. The overall objective of this grant is to gain insight into the genes, proteins and hormonal signaling networks that govern normal testicular development, testicular descent and their role in human disease. Testicular torsion, affecting 1 in 4,000 males younger than 25 years of age, is the spontaneous rotation of the testicle which can result in death of the testicle. This is likely due to abnormal testicular development. In addition, cryptorchidism, the absence of the testicle from the scrotum, is the most common genital anomaly of male infants affecting 3% at birth. Given the increasing incidence of cryptorchidism and the frequent occurrence and significant morbidity associated with testicular torsion and cryptorchidism, a deeper understanding of the mechanisms of testicular development has emerged a key issue. The recently identified testicular hormone lnsulin-3 (InsIS), and its recently identified G-protein coupled receptor, GREAT/LGR8, are crucial to normal murine testicular descent. However, the role of this hormonal pathway has not been thoroughly investigated in humans. To address this need, 3 specific aims are proposed: 1) To investigate the functional significance of InsIS and GREAT/LGR8 in human cryptorchidism; 2) To explore the role of altered InsIS signaling as a cause of testicular torsion in mice and humans; and 3) To perform preclinical murine studies investigating the role of InsIS as a drug therapy for the treatment of cryptorchidism. By integrating strong developmental biological basic science employing genetically engineered mouse models with research on affected humans, the overall goal of this highly collaborative investigation is to advance our knowledge of the hormonal pathways controlling testicular development.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD048838-01A1
Application #
6969441
Study Section
Integrative and Clinical Endocrinology and Reproduction Study Section (ICER)
Program Officer
Taymans, Susan
Project Start
2005-08-10
Project End
2010-05-31
Budget Start
2005-08-10
Budget End
2006-05-31
Support Year
1
Fiscal Year
2005
Total Cost
$304,200
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Urology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
DaJusta, Daniel G; Granberg, Candace F; Villanueva, Carlos et al. (2013) Contemporary review of testicular torsion: new concepts, emerging technologies and potential therapeutics. J Pediatr Urol 9:723-30
Cost, Nicholas G; Bush, Nicol C; Barber, Theodore D et al. (2011) Pediatric testicular torsion: demographics of national orchiopexy versus orchiectomy rates. J Urol 185:2459-63