The outer layer of the corpus cavernosum, the tunica albuginea, is rich in elastic fibers and has the capacity to expand in response to the force of blood pressure, resulting in an increased length and diameter of the penis. However, the expandability of the tunica is finite, and ultimately the initial rise in intracavernosal pressure (ICP) along with the opposing force of the tunica albuginea activates a mechanical occlusion or "sandwiching" of the venous outflow. Thus, the combined inflow of blood following penile arteriole and sinusoidal dilation, as well as subsequent veno-occlusion, result in maintained elevation of ICP and erection. We recently found that Db/db mice, a common mouse model of type II diabetes, have a veno-occlusive disorder that stems from a lack of tissue filling due, in part, to altered vasoreactivity consistent with impaired cavernosal relaxant ability. We also showed that these mice have may impairment in tissue distensability resulting from altered deposition of fibrillar collagen and elastin. Elastic fibers are assembled extracellularly and are comprised of elastin and specific microfibrillar proteins. Unlike most proteins, elastin production is limited to a brief period of development, beginning during fetal growth and peaking during early neonatal periods. Thereafter, elastin production declines rapidly. By maturity, assembly of elastic fibers is complete, and synthesis of new tropoelastin, the soluble precursor, has declined. Certain diseases, however, such as pulmonary hypertension and emphysema, are characterized by an abnormal accumulation of elastin or by an inability to re-initiate elastin production in response to injury. Still other diseases, such as Marfan's syndrome and cutis laxa, arise from mutations in genes that support elastin organization. In this proposal, we hypothesize that elastin deposition and fiber formation is critical for proper erectile function and that this process is altered in type II diabetic mice, resulting in impaired veno-occlusive function and erectile dysfunction. As elastin degradation is also known to occur in tissue following smoking and/or aging, this knowledge gained from this proposal may also have implications for erectile dysfunction associated with these risk factors as well.

Public Health Relevance

Erection is dependent on distensability of the penis which is enabled by the abundance of elastin in the tunica albuginea and sinusoids. We hypothesize that disruptions in elastin content and elastic fiber organization contribute to erectile dysfunction associated with type II diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK082560-04
Application #
8268132
Study Section
Urologic and Kidney Development and Genitourinary Diseases Study Section (UKGD)
Program Officer
Rankin, Tracy L
Project Start
2009-03-24
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
4
Fiscal Year
2012
Total Cost
$353,866
Indirect Cost
$140,694
Name
University of Washington
Department
None
Type
Other Domestic Higher Education
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Hidalgo-Tamola, Josephine; Luttrell, Ian; Jiang, Xiaogang et al. (2011) Characterization of erectile function in elastin haploinsufficicent mice. J Sex Med 8:3075-85