HMS Researchers Discover Puberty Gene

Nine Harvard Medical School affiliates are among a group of researchers that have identified a gene necessary for the onset of puberty in mice—and men.

The discovery, described in a study published yesterday in the New England Journal of Medicine, will aid scientists in understanding and treating reproductive disorders.

In the study, the researchers identified one genetic factor that they observed as a trigger of sexual development.

The study was a combined effort of the Medical School researchers and representatives from Paradigm Therapeutics, a genetic engineering company based in Cambridge, England.

The scientists found that certain mutations of a gene called GPR54 will inhibit the onset of puberty in both mice and humans. The Harvard research team studied the genetic material of humans presenting this condition, which is far more likely to be found in individuals with closely blood-related parents.

The findings are significant for a field whose major goals include targeting and identifying new genes, said Stephanie B. Seminara ’87, one of the Medical School researchers affiliated with the study.

“Certainly there is a wonderful sense of personal fulfillment, but also tremendous excitement at having discovered a new pathway in reproductive biology,” said Seminara, who is also a member of the Reproductive Endocrine Unit at Massachusetts General Hospital (MGH).

Prior to this research, the gene in question was largely unknown and thought to be relevant only in the sphere of cancer research. However, Seminara said, “[the study] suggests that this gene is operating at the top rung of reproductive biology.”

Researchers will continue studying the identified gene, analyzing its specific qualities.

“Ultimately, we’ll be looking at our research data with an eye for developing new and improved therapies for patients with a variety of reproductive disorders,” Seminara said.

The Medical School researchers began their study, funded by the National Institutes of Health, two and a half years ago. Their subjects came from a Saudi Arabian family in which two cousins had married and produced several children who failed to undergo puberty.

After extended analysis, researchers at MGH were able to link the condition to a mutation on a certain chromosome. Upon hearing of these findings, representatives of Paradigm Therapeutics notified the Boston-based team that they had detected the same condition in mice that had been engineered without a gene that lay on the same chromosome.

The study is also historic for the New England Journal of Medicine, as the article marks the Journal’s first publication of findings derived from animal data.

Of the Harvard-affiliated researchers, six are affiliated with MGH, including Seminara, William F. Crowley Jr., James F. Gusella, Susan A. Slaugenhaupt, Jenna K. Shagoury and James S. Acierno. Two other researchers, Wendy Kuohung and Ursula B. Kaiser, are affiliated with Brigham and Women’s Hospital.