The dream of many family planners is a birth control pill for men, something that would somehow shut off sperm production but leave sex drive and beards intact. For years, researchers have targeted follicle-stimulating hormone (FSH) for this delicate task. This hormone ripens eggs in females and has long been thought to do the same for sperm--without affecting levels of the male sex hormone, testosterone. But now a pair of papers to be published in this month's issue of Nature Genetics suggests a fatal flaw in any birth control method that relies on curbing FSH alone: Developing sperm don't need it to become potent.
Martin Matzuk, an endocrinologist at Baylor College of Medicine in Houston, began studying FSH for another reason: to investigate the hormone's role in ovarian cancer. He and his colleagues created genetically engineered mice that lack the gene coding for FSH. When they mated the adult mice, the females had no hormones to develop their eggs and were infertile. But the males--despite having smaller testes and lower sperm counts than normal mice--were clearly fertile and produced offspring. "It's been a real surprise to people," says Matzuk. "The dogma was that FSH is required to make sperm. That's what the textbooks say."
Matzuk's results are backed up in a companion paper by a Finnish team studying FSH mutations in humans. Juha Tapanainen of Oulu University Hospital in Oulu and colleagues at the University of Helsinki studied 15 brothers of infertile women who had mutations in the gene coding for the FSH receptor. Although the men with the mutant genes produced FSH, support cells for the sperm-producing cells in their testes lacked the receptors for the hormone. Five of the men shared the symptoms of the mice--small testes and reduced sperm count--but two of the five had fathered children.
FSH does play a role in making sperm by stimulating Sertoli's cells, which provide nutrients to the growing sperm cells, says Matzuk. Without these helper cells, the testes are smaller and make fewer sperm. But the Finnish researchers believe that testosterone itself can partially compensate for the lack, thus subverting any birth control pill designed to eliminate FSH. "The moral is, you have to come up with something to do a better job of suppressing sperm count," says Bill Bremner, a reproductive endocrinologist at the University of Washington. With FSH and a one-step contraceptive for men out of the picture, researchers must now concentrate on a more complicated hormonal balancing act between FSH, testosterone, and other reproductive hormones.