Lab study offers clues for drug development
Men have a four times greater risk than women of developing abdominal aortic aneurysms, estimated to be the cause of death in 4 percent of people over the age of 65, but the mechanism for this higher incidence has remained unknown. Researchers at the University of Kentucky now report evidence that the answer lies in male sex hormones. They found that removing circulating androgens, including testosterone and dihydrotestosterone, from male mice lowers their risk of aneurysm to that of females, while giving females these same male sex hormones increases their risk to that of males.
Tracy Henriques, a graduate student in the laboratories of Drs. Lisa Cassis and Alan Daugherty, presented the study Monday, April 4, at the American Society for Investigative Pathology scientific sessions at Experimental Biology 2005 in San Diego.
In a well-established research method, giving hyperlipidemic mice the peptide hormone angiotensin II results in the development of abdominal aortic aneurysms. Not surprisingly, considering the gender differences in humans, male mice have a three-fold higher susceptibility to developing the angiotensin-induced aneurysms than age-matched females receiving the same drug. Recent studies in the Cassis/Daugherty laboratories revealed that removing the male sex hormones reduced the incidence of aneurysms in male mice to the same lower levels seen in the females.
In this new study, the researchers found that giving male sex hormones to female mice at the time of the angiotensin infusion turns the females into males in terms of their susceptibility. Administration of testosterone raised the incidence of developing abdominal aortic aneurysms by 55 percent in the females; dihydrotestosterone raised the incidence to 67 percent. In addition, the females given male sex hormones developed more severe aneurysms compared to placebo treated female mice.
The goal of the laboratory now is to find the target of the male sex hormones that mediates these differences, in the hopes of developing drugs that can be used to lower incidence of the life-threatening aneurysms, say Drs. Cassis and Daugherty. Currently no pharmacologic treatments exist with proven efficacy to treat aneurysms. The only existing treatment is surgery when the risk of death due to possible rupture of the abdominal aortic aneurysm is judged to outweigh the risk of surgery.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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