Scientists unravel clue in cortisol ...( ns were interacting both with each oth...)

"One of the best ways to try and figure out the function of a protein or a gene is to get rid of it or mutate it so that it's not acting normally. Then you compare it with one that is acting normally," said Sewer.

In this study, they focused on a protein known as steriodogenic factor 1 (SF-1), which is essential for making all steroid hormones. Researchers were interested in discovering what events have to occur in order for SF-1 to bind to DNA.

The first thing they found was that because DNA is so tightly packed in the nucleus, SF-1 can't bind to it until it's unpacked by a group of proteins. Once that happens, SF-1 binds to the genes, beginning the process that makes CYP 17 and ultimately cortisol. But it's not a continuous process, they found.

"Once SF-1 binds, it leaves. A few minutes later other proteins come in and condense the DNA," said Sewer. "After that SF-1 binds again, then leaves, and the proteins cause the DNA to contract again."

This cycle goes on as long as the adrenal gland is receiving the signal.

"Even though you get a sustained production of cortisol, the actual molecular events that happen in the nucleus are dynamic," said Sewer. "It's an extremely complex series of events that starts within minutes of the adrenal gland receiving the signal. Without all these transient binding events, the adrenal gland fails to produce optimal levels of cortisol."

Next the team will investigate how small molecules ligands regulate cortisol production by binding to SF-1 and controlling the receptor's ability to bind to DNA.

'"/>

Contact: David Terraso
d.terraso@gatech.edu
404-385-2966
Georgia Institute of Technology
24-Apr-2007