alexa Dihydrotestosterone promotes vascular cell adhesion molecule-1 expression in male human endothelial cells via a nuclear factor-kappaB-dependent pathway.
Diabetes & Endocrinology

Diabetes & Endocrinology

Journal of Steroids & Hormonal Science

Author(s): Death AK, McGrath KC, Sader MA, Nakhla S, Jessup W,

Abstract Share this page

Abstract There exists a striking gender difference in atherosclerotic vascular disease. For decades, estrogen was considered atheroprotective; however, an alternative is that androgen exposure in early life may predispose men to earlier atherosclerosis. We recently demonstrated that the potent androgen, dihydrotestosterone (DHT), enhanced the binding of monocytes to the endothelium, a key early event in atherosclerosis, via increased expression of vascular cell adhesion molecule-1 (VCAM-1). We now show that DHT mediates its effects on VCAM-1 expression at the promoter level through a novel androgen receptor (AR)/nuclear factor-kappaB (NF-kappaB) mechanism. Human umbilical vein endothelial cells were exposed to 4-400 nm DHT. DHT increased VCAM-1 mRNA in a dose- and time-dependent manner. The DHT effect could be blocked by the AR antagonist, hydroxyflutamide. DHT increased VCAM-1 promoter activity via NF-kappaB activation without affecting VCAM-1 mRNA stability. Using 5' deletion analysis, it was determined that the NF-kappaB sites within the VCAM-1 promoter region were responsible for the DHT-mediated increase in VCAM-1 expression; however, coimmunoprecipitation studies suggested there is no direct interaction between AR and NF-kappaB. Instead, DHT treatment decreased the level of the NF-kappaB inhibitory protein. DHT did not affect VCAM-1 protein expression and monocyte adhesion when female endothelial cells were tested. AR expression was higher in male, relative to female, endothelial cells, associated with increased VCAM-1 levels. These findings highlight a novel AR/NF-kappaB mediated mechanism for VCAM-1 expression and monocyte adhesion operating in male endothelial cells that may represent an important unrecognized mechanism for the male predisposition to atherosclerosis. This article was published in Endocrinology and referenced in Journal of Steroids & Hormonal Science

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Peer Reviewed Journals
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version