Discovery Hints At Multitude Of New Targets For Drugs

DURHAM, N.C. -- A new study of how drugs plug into the human progesterone receptor in the cell supports a new and different view of how drugs and hormones act on steroid hormone receptors that trigger cellular responses.

The new view holds that steroid receptors are not merely on-off switches, but are far more complicated molecular "control panels" that could be manipulated by drugs customized to produce more targeted effects on the body, said the scientists who made the discovery. The drugs could cause the same receptor to trigger only certain of its normal effects in the body, but not others.

The finding, if confirmed, could point the way to a new wave of drugs with fewer side effects for contraception, hormone replacement therapy, breast and prostate cancer, inflammation, osteoporosis and endometriosis, said the researchers.

The scientists published their findings in the Aug. 6 issue of the Proceedings of the National Academy of Sciences. They are Brandee Wagner, Giuseppe Pollio and Donald McDonnell of the Duke University Medical Center departments of pharmacology and molecular cancer biology; Mansukh Wani, David Lee and C. Edgar Cook of the Research Triangle Institute (RTI), and Susan Leonhardt and Dean Edwards of the University of Colorado Health Science Center department of pathology. Their research was supported by the U.S. Public Health Service.

The researchers used living cells and test tube preparations to analyze how a range of compounds known to plug into the progesterone receptor affected its action.

Compounds that plug into receptors are known as ligands. Steroid receptors are complex proteins that are the principal switches activating cellular responses to steroid hormones. Steroid receptors reside deep in the cell's nucleus, activating genes that produce cellular responses. When a hormone or drug plugs into a receptor, that action changes the shape, or conforma

Contact: Karyn George
Duke University

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