PITTSBURGH, PA -- Ethanol is the active ingredient in all alcoholic beverages including beer, wine and hard liquor. Ingestion of fermented beverages containing ethanol has been known since the beginning of recorded history. Ethanol was first thought to have strong medicinal properties but now it is acknowledged that chronic consumption of excessive amounts of alcohol is a major source of social and medical problems.
Researchers have established that chronic ethanol is a depressant drug that disturbs the normal chemical actions of nerve cells resulting in reduced efficiency of neural impulse conductance. Additionally, excessive consumption can lead to various biochemical and intracellular changes that may cause alcohol–induced liver injury. Men and women who chronically consume ethanol may have different susceptibility to the alcohol’s damage to their liver due to altered expression of genes related to liver function. To test that assumption, University of Pittsburgh researchers set out to determine sex-specific expression of genes in the livers of rats chronically fed alcohol.
The authors of the study, “Gender Differences in Hepatic Gene Expression in Response to Chronic Ethanol Exposure,” are P.K. Eagon, Ph.D., M.S. Elm, H.S. Li, G.J. Van Londen, D.C. Whitcomb, and S.D. Tadic, all from the VA Medical Center and the Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA. Their findings are being presented at the upcoming conference, Genomes and Hormones: An Integrative Approach to Gender Differences in Physiology, being sponsored by the American Physiological Society (APS), and held October 17-20, 2001, at the Westin Convention Center, Pittsburgh, Pa.
Methodology and Results
Rats were fed diets containing alcohol or alcohol-free diets for 30 days to induce fatty liver with minimal necrosis and inflammation. Microarray analysis was performed to determine differences in gene expression using a toxicology array.
Different gene were expressed in rats consuming alcohol compared to those which did not and expression of twenty-nine genes were changed only in male rats; expression of six genes changed only in female rats, and nine separate genes changed in both males and females. The genes encode proteins that cover a spectrum of liver cellular functions including production of protein and immunological responses. Expression of genes which changed in male rats were also regulated by androgens (the generic term for the predominating male hormone) While in female rats, genes affected by alcohol were also changed by the female hormone, estrogen.
Other genes changed in both genders but in opposite ways. For example, expression of several genes coding for hepatoprotective proteins were increased in males but decreased in females.
Conclusion
This study suggests a mechanism for sex differences in alcohol-related injury such that in female animals expression of genes that offer protection to the liver do not increase to the same extent as in males. The authors conclude that with long-term heavy use of alcohol, the inability of females to induce protective mechanisms will place females at higher risk of liver damage when both genders drink equal amounts of alcohol.
The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.
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Contact: Donna Krupa:
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The Westin Convention Center
Pittsburgh, PA
October 17-20, 2001
Tel: 412.281.3700 (The Crawford Room)