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Research may speed development of new oral drugs for fertility treatments

Researchers now have a much better picture of how follicle-stimulating hormone (FSH), one of the most frequently used fertility drugs, works, and with it new ideas for creating a new generation of oral medications to treat infertility.

The exquisite detail of the images produced by Howard Hughes Medical Institute (HHMI) investigator Wayne A. Hendrickson and colleague Qing Fan begins to tell for the first time how the FSH hormone attaches to a key segment of its receptor on the cell surface. The binding of the hormone to its receptor then stimulates the maturation of ovarian follicles in women or sperm production in men.

Insights gleaned from this structure could aid in the development of improved fertility drugs or contraceptives for both men and women. Hendrickson and Fan, who are both at Columbia University, reported the details of the structure in an article published in the January 20, 2005, issue of the journal Nature.

"Although the nature of FSH and other glycoprotein hormones has been known for more than 30 years, there is still no orally active therapeutic drug," wrote James A. Dias of the Wadsworth Center in a commentary in the journal Nature. "But such a drug might one day be developed, thanks to the findings presented by Fan and Hendrickson."

"The crystal structure of FSH in complex with the FSH receptor extracellular domain is a major achievement in the field of glycoprotein hormones and G-protein coupled receptors," said Dias in an interview. "For ten years we have had the 'key.' That is, the crystal structure of the hormone.... Now we not only have the lock, but the key in the lock," he said.

Researchers are equally excited by the architectural blueprint of FSH and its receptor because it may help unravel the structural framework of a trio of other hormones, notably, luteinizing hormone (LH), chorionic gonadotropin (CG), and t
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
19-Jan-2005


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