Quick study: A glowing reception
THE QUESTION: Could there be a noninvasive way to quickly screen how various drugs and hormones interact with the estrogen receptor inside living cells and animals?
THE BACKGROUND: Estrogens are hormones responsible for growth and maintenance of many systems in the body. In both men and women, its effects are mediated through the estrogen receptor. Too much or too little estrogen can lead to disease, including osteoporosis, heart disease and breast cancer, making the search for drugs that can modify the estrogen receptor's responsiveness an attractive target for therapeutic interventions.
THE STUDY: Past studies have shown that when a small molecule "key" docks with the estrogen receptor "lock," a kind of molecular switch either suppresses or enhances the receptor's activity. The researchers combined this detailed structural information with noninvasive molecular imaging techniques. They devised a way of attaching split molecules of luciferase—an enzyme that is capable of producing light—onto ends of the estrogen receptor protein. If the appropriate drug docked with estrogen receptors in cultured cells or live mice, the pieces of the luciferase would come together and generate a measurable glow.
THE FINDINGS: By the amount of glow ing light generated, the sensor immediately indicated compounds that enhanced the activity of the estrogen receptor and those that suppressed it.
WHY IT MATTERS: This is the first in vivo sensor of this kind, using protein folding to reveal receptor activity of any sort. The researchers predict that this method will eventually provide a better way to screen for a compound's interaction with the estrogen receptor, which could mean a quicker path to developing drugs that alter the receptor's activity. It also can be modified to include study of other receptor systems.
CAVEAT: This method has only been tested in mice.
FIND THIS STUDY: This study is published in the online Oct. 9 version of Proceedings of the National Academy of Sciences, available at http://www.pnas.org/.
STANFORD CONNECTION: First author Ramasamy Paulmurugan, PhD, is a physical sciences associate in radiology. The study's senior author is professor of radiology and of bioengineering Sam Gambhir, MD, PhD, who also heads the division of nuclear medicine and the molecular imaging program.