The master cells of fertility, a tiny population of neurons that trigger the production of eggs and sperm, now can be raised in the laboratory, a feat of biological wizardry that scientists say raises expectations for a new generation of drugs to treat infertility or control unwanted births.
According to new research presented yesterday, these neurons appear to operate on a timetable all their own, releasing a pulse of hormones that sets off a cascade of events central to reproduction, including the release of a mature egg from the ovaries and the production of viable sperm. These brain cells are also responsible for the onset of puberty.
Now, for the first time, researchers can study these cells in detail in the laboratory, where they continue to gush out hormones like clockwork even after they have been removed from the body and placed in a dish.
Scientists believe that by understanding the mechanism by which these neurons time the release of their hormones, they can learn how the body sets its reproductive clock and how modern medicine could intervene to correct infertility or devise better birth control methods.
"If one could understand the pulse of these cells, the timing, one could modify it," said Pamela Mellon of the Salk Institute in California, whose work with colleague Richard Weiner of the University of California at San Francisco was presented yesterday in St. Louis at the annual meeting of the Society for Neuroscience.
Weiner and Mellon were the first to successfully remove "fertility cells" from the brain of a mouse and grow them indefinitely in the lab. The mouse cells work the same way as those found in humans, but run on a faster cycle, secreting hormones every 20 minutes. In women, the hormone-emitting alarm clock rings either every hour or every four hours, depending on the stage of the menstrual cycle. In men, the cells release hormones every hour.
The neurons that Weiner and Mellon are studying come from a tiny population of 1,500 cells in the brain's hypothalamus, a pea-sized structure often referred to as "the brain within the brain," which regulates eating, drinking, sleeping, waking, body temperature, heart rate, emotions, hormones and sex. The cells are a very small fraction of the approximately 100 billion cells in the average human brain.
These cells release a substance known as "gonadotropin releasing hormone," which researchers long have known is essential for fertility. After its release, gonadotropin releasing hormone travels a short distance from the hypothalamus to the pituitary gland at the base of the brain, which produces secondary hormones that travel to the ovaries and testes with instructions to start releasing eggs or making sperm.
What Weiner and Mellon have found is that the master fertility cells appear capable of secreting their hormone independently, without the need for an additional signal. Weiner calls this rhythm "the basic cadence" of fertility. Other neurons in the brain can speed up the rhythm or change its amplitude, but the rhythm appears to be inherent in the cells.
How they do this is unknown, though the cells adjoin one another and appear to be in communication.
"These cells behave with tremendous fidelity," Weiner said. "There is an incredible amount of machinery programmed in. They make the hormone and they release it in a very coherent, very regulated pulse. It is a fascinating system."