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Scientists unravel clue in cortisol production

When a person's under stress or injured, the adrenal gland releases cortisol to help restore the body's functions to normal. But the hormone's effects are many and varied, lowering the activity of the immune system, helping create memories with short-term exposure, while impairing learning if there's too much for too long. Given the variety of its effects,understanding how cortisol is made is essential to producing medications that can alter its production.

Scientists at the Georgia Institute of Technology have discovered an important step in cortisol production, finding that although the output of the hormone is continuous, the molecular production is cyclic in nature ?involving a rhythmic binding and unbinding of a protein essential to its production. The research, which increases understanding of how the brain and the endocrine system work together to regulate health, appears in the February issue of the journal Molecular Endocrinology.

Turning cholesterol into the stress hormone cortisol involves many reactions and begins when the hypothalamus sends a signal to the adrenal glands. Proteins then flood into the nucleus to bind to the DNA, creating the gene CYP 17. What happens next is well understood; CYP 17, along with a battery of other enzymes, transforms cholesterol into cortisol. But what isn't understood is how this protein binding creates CYP 17, or which proteins are important. So, graduate students Eric Dammer and Adam Leon, along with Marion Sewer, assistant professor in Georgia Tech's School of Biology, decided to model the events that occur after the adrenal gland receives the signal.

One of the things the signal does is cause adrenal cells to increase their production of cyclic AMP (cAMP), a chemical that encourages proteins to interact. So they began by causing the cells to make more cAMP. Then as the proteins assembled on the DNA, they tested the cells at different intervals in order to get a snapshot of which proteins wer
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Source:Georgia Institute of Technology


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