Researcher finds new role for zebrafish in human studies

May 19, 2010

Michael E. Baker, PhD, a researcher at the University of California, San Diego School of Medicine has discovered that zebrafish - an important animal model in disease and environmental studies - could provide the means to help scientists eventually reveal the function of a mysterious enzyme linked to the steroid cortisol, and found in the human brain.

In people and other vertebrates, steroids like cortisol perform a variety of diverse duties, including regulating immune response, bone formation and . Too much cortisol, however, is unhealthy. High levels of the steroid have been linked to and may impair the brain's ability to store memories.

The human body regulates cortisol by employing an enzyme called 11 beta-hydroxysteroid dehydrogenase-type 1 or 11beta-HSD1, which catalyzes the synthesis of cortisol in liver and . A related enzyme known as 11 beta-HSD-type3 or 11 beta-HSD3 is expressed in the brain, though its utility remains unknown.

In new findings to be published in the June 3 issue of FEBS Letters, Baker, a research professor of medicine who works in the division of nephrology-hypertension at UC San Diego's School of Medicine, reports that 11 beta-HSD3 (but not 11 beta-HSD1) is present in zebrafish, where it appears to serve an important role in fish endocrine physiology.

That makes the fish a potentially useful analog for studies, including discovering the purpose and function of 11 beta-HSD3 in human brains, which may be an evolutionary precursor to 11 beta-HSD1.

Interestingly, Baker found that the genomes of mice and rats do not contain 11 beta-HSD3, which means that inserting the appropriate gene for the enzyme in these animal models could provide additional avenues of investigation.

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