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Worm hormone discovery may aid fight against parasitic disease

New research at UT Southwestern Medical Center shows that on a biochemical level, hormone-like molecules in tiny worms called nematodes work similarly to the way in which certain hormones work in humans ?findings that one day may help eradicate worm infections that afflict a third of the world's population.

UT Southwestern researchers have discovered a molecule that activates genes involved in the development and reproduction of Caenorhabditis elegans, a common research worm about the size of a pinhead.

In a study available online and appearing in the March 24 issue of the journal Cell, UT Southwestern scientists describe how the molecule, called a ligand, acts like a hormone, the first such hormonal ligand identified in C. elegans.

Like a key fitting into a lock, the newfound ligand binds to a protein in the cell's nucleus called a nuclear receptor, a receptor designated DAF-12. Once that binding occurs, DAF-12 activates other genes that allow the worm to develop through its normal stages, reach maturity and reproduce.

When the researchers blocked that hormonal signal by engineering mutant worms that couldn't manufacture the ligand, however, the mutants' development stopped before they reached maturity. Instead, the worms went into a "resting" stage called the dauer diapause, in which they don't eat or reproduce. When the researchers provided the mutants with the missing ligand, it prevented the dauer stage, and the animals continued to develop normally.

"This pathway in worms is remarkably similar to hormonal pathways in humans," said Dr. David Mangelsdorf, chairman of pharmacology at UT Southwestern and senior author of the study.

The experiments by Dr. Mangelsdorf's team are related to how hormone-replacement therapy works in humans. For example, in patients with Addison's disease, the adrenal glands do not produce enough of the steroids cortisol and aldosterone; in some cases, these glands produce none at all. Re
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Source:UT Southwestern Medical Center


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