Three dimensional structure of FSH is detailed - could lead to new drug forms

Last published /updated 1/22/2005 Whenever you see a publication in the journal Nature, expect something big and important. This is no exception. Wayne A. Hendrickson and his colleague Qing Fan of the Howard Hughes Medical Institute (HHMI) have created detailed images of the reproductive hormone FSH - follicle stimulating hormone and its receptor. FSH is the hormone which is created in the pituitary and when secreted into the bloodstream serves to stimulate the ovaries or testicles. Like all hormones, FSH "connects" with a receptor on a cell. This "connection" causes changes in the cell that accomplishes some function. Until now, researchers did not understand key details about how FSH interacts with its receptor, largely because the complex had never been crystallized and examined at the molecular level. These researchers set out to produce crystals of the complex to use in determining its structure using a method called x-ray crystallography. With this technique, x-rays are directed through crystals of a protein to be analyzed. The patterns that result are then analyzed using computers to deduce the structure of the molecule under study. So why should you care about this? Well the key to understanding how hormones work is understanding where and how they act on their receptors. Once this is understood, scientists can devise derivatives. FSH is available as a fertility medication under the trade name Gonal-F or Follistim. It is administered as a subcutaneous injection on a daily basis. With greater understanding, you might be able to create a variant of the hormone that acts for a longer period time. What if it were possible to give FSH only once a month and still get the same effect? How great would that be? Another possibility is the creation of orally active FSH medications. Currently this is impossible because FSH which is a protein gets broken down in the stomach. Of course, none of this will happen overnight but it is a major breakthrough that will yield benefits for years to come.