A new generation of oral fertility drugs could be on the horizon, thanks to research into the inner workings of a well-known hormone. Follicle stimulating hormone is one of the most commonly prescribed drugs used in assisted reproduction.
Along with luteinizing hormone (LH), follicle stimulating hormone (FSH) is produced naturally by the body to control the reproductive cycles of both men and women. They are made by the pituitary gland, a small gland located directly below the brain. FSH is also produced as a medication. Marketed as Bravelle, Follistim or Gonal-F, the medication stimulates the ovaries to produce follicles.1
Now for the first time, researchers have uncovered some of the mechanisms behind how this hormone works. The findings are published in the January 20 issue of the journal Nature.2
How FSH Interacts with Cells
The study focused on the ways the FSH hormone attaches to a receptor on the surface of certain cells in the body. Receptors are proteins on the surface of cells that have a special affinity, or relationship, to something outside the cell—in this case, FSH. When a substance like FSH binds with this molecule on the surface of a particular cell, it causes that cell to take action in some way. In this case, scientists say FSH attaches to its cell-surface receptor, which in turn, causes follicles to begin maturing, the precursor event to the release of an egg.
In men, when FSH attaches to its receptor on the surface of sperm cells, sperm production is launched.
Insights behind this process involving FSH could aid in the development of improved fertility drugs for both men and women, experts predict. "Although the nature of FSH and other hormones has been known for more than 30 years, there is still no orally active therapeutic drug," wrote James Dias, PhD, a research scientist at the Wadsworth Center, a division of the New York Health Department, in a related editorial.3
"But such a drug might one day be developed, thanks to the findings [of this study]," Dias wrote.
Breaking into the Unknown
Until now, medical scientists did not understand how FSH interacted with its receptor, largely because experts could not study it at the molecular level. But Wayne Hendrickson, PhD, and colleague Qing Fan at the Howard Hughes Medical Institute at Columbia University first produced a unique way to view the structure of this intriguing hormone. They then were artificially able to reproduce the process by which FSH binds to reproductive cells.
Many previous studies contributed pieces to the puzzle of how FSH plugs into its receptor on the surface of cells, admitted the two scientists. But they say their work helped fill gaps in knowledge.
Zeroing in on the Cellular Relationship
Next, they plan to study the ways receptors on the surface of reproductive cells signal FSH and other hormones, the first step in the eventual attachment of the hormones to their receptors.
Though he wasn't trained as a clinician, Hendrickson says he is keenly aware of the clinical implications of this study. "FSH is already being used to stimulate ovulation in women who are infertile, and to enhance [sperm production] in men," he said. "Knowing the details of the hormone-receptor structure could enable modifications to FSH used in treatment to make it more potent and longer-lived in the bloodstream."
1. Boston IVF. Fertility Medications and IUI. Available at: http://www.bostonivf.com/undergoing_treatment/
fertility_medication_iui.cfm#3. Accessed February 8, 2005.
2. Fan QR, Hendrickson WA. Structure of human follicle-stimulating hormone in complex with its receptor. Nature 2005 Jan 20;433(7023):269-77.
3. Dias JA. Endocrinology: fertility hormone in repose. Nature 2005 Jan 20;433(7023):203-4.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
