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First 'encyclopedia' of nuclear receptors reveals organisms' focus on sex, food

In creating the first "encyclopedia" of an entire superfamily of nuclear receptors ?proteins that turn genes on and off throughout the body ?UT Southwestern Medical Center researchers found that certain receptors form networks and interact to regulate disease states and physiology in two main areas, reproduction and nutrient metabolism.

Receptor networks also have key roles in metabolism's biological clock, researchers found.

The findings, published today in two studies in the journal Cell, chart the anatomy and timing of nuclear receptor expression throughout the body in hopes that researchers can uncover global receptor functions to improve prediction, diagnosis and treatment of diseases, from hypertension to diabetes.

"This 'systems biology' approach to look at the whole superfamily, not just individuals, is a new way to understand how nuclear receptors regulate physiology," said Dr. David Mangelsdorf, chairman of pharmacology and senior author of one study. "Remarkably, receptors break into two big clusters centered on reproduction and metabolism. So it really is all about sex and food.

"The power of this analysis is highlighting such receptor associations that may predict functions heretofore unknown. This really is pointing to new directions in biology."

Much already is known about individual nuclear receptors, which are proteins found in cell nuclei in reproductive, digestive and liver, immune, and many other tissue systems. Such receptors act as sensors for hormones and dietary molecules, binding to them to trigger gene expression.

Individual nuclear receptors are among the most successful targets for drugs currently available or being developed to treat a number of conditions, including reproductive disorders, cancer, diabetes, cardiovascular disease and high cholesterol. But how receptors work together to impact physiology has been largely unknown.

To find out, researchers from UT Southw
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Source:UT Southwestern Medical Center


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