Scientists have caught a glimpse of what they call the "pilot light of reproduction," identifying for the first time a gene that plays a role in triggering puberty. The research provides a new tool to help understand the complex processes that cause humans to mature, well, at least sexually.
Puberty begins when a part of the brain called the hypothalamus begins pumping out gonadotropin-releasing hormone (GNRH) which in turn prompts the gonads to develop and the body to change. Not much is known about the genes and cellular pathways that trigger GNRH release. Scientists have identified genes that are active during puberty, but most also have key functions in other basic processes, such as regulating fat. Few seem specifically related to puberty.
Hoping to identify the genetic switch for puberty, endocrinologist Stephanie Seminara of Harvard Medical School in Boston and her team studied a Saudi Arabian family, some members of which don't go through puberty. Without treatment, neither sex develops characteristics of sexual maturity. The men's voices don't deepen, for example, and women often don't develop breasts. They discovered that those with the disorder had mutations on a specific gene, called GPR54, which is known to produce a receptor in cell membranes. They also found that unrelated patients with the same condition had different mutations that stopped GPR54 from doing its job.
Further confirmation of the gene's role in puberty comes from researchers at Paradigm Therapeutics in Cambridge, U.K., who created mice that lacked the gene. As expected, the engineered mice didn't go through puberty. They did mature when given GNRH. The mice had GNRH in their hypothalamus, suggesting that the mutated gene doesn't prevent the hypothalamus from making GNRH, but somehow prevents it from secreting the hormone, the two teams report in the 23 October issue of The New England Journal of Medicine.
"This study opens the door to a whole new area that may give us an understanding of what causes puberty," says endocrinologist Michael Conn of Oregon Health and Science University in Portland. But before the new knowledge can be turned into treatments, he says, researchers will have to figure out exactly what the gene does in the process that sparks maturity.