Yale University researchers have visualized in atomic detail how two important female sex hormones, progesterone and estrogen, bind to their receptors—an accomplishment that could help scientists design better medications to treat breast cancer, ease the symptoms of menopause and prevent unwanted pregnancies.

The Yale scientists’ data are available to the worldwide research community through the Protein Data Bank at Brookhaven National Laboratories on Long Island. Paul B. Sigler, M.D., Ph.D., professor of molecular biophysics and biochemistry, and his colleagues are the first to make the structure of the estrogen-receptor complex available to scientists through the data bank.

Dr. Sigler’s detailed atomic comparison of the estrogen and progesterone receptors binding—prepared in collaboration with Yale graduate student David M. Tanenbaum and postdoctoral associates Shawn P. Williams, Ph.D., and Yong Wang, Ph.D.—was published in the May 26 issue of the Proceedings of the National Academy of Sciences. A separate report by Dr. Sigler and Dr. Williams on the progesterone receptor alone was published May 28 in the journal Nature.

Drugs such as tamoxifin and raloxifene that bind to the estrogen receptor and block the uptake of estrogen have been shown in recent studies to be effective in treating and even preventing breast cancer. However, even more effective estrogen blockers could be created using the three-dimensional, computerized “snapshot” of the estrogen receptor captured at Yale, said Dr. Sigler, a Howard Hughes Medical Institute investigator at Yale. Tailor-made medications that improve the uptake of estrogen instead of blocking it could help relieve menopausal symptoms.

“Our work with the progesterone receptor has given us by far the highest resolution, that is, the clearest look we have ever had, of the chemistry that underlies a steroid binding to its receptor,” said Dr. Sigler. Using a technique called X-ray crystallography, the researchers generated an image of progesterone bound snugly in its receptor’s specific binding pocket at a resolution of 1.8 angstroms, which is roughly the distance between two atoms.