Health & Parenting

Puberty Gene Found

Oct. 22, 2003 -- Harry Potter mice are more like Peter Pan than the boy wizard. Why? They won't grow up.

The mice won't mature sexually because they lack a crucial gene. Some humans who never hit puberty have mutant forms of the same gene. Dubbed Gpr54, the gene appears to be a key part of the mysterious machinery that turns children into adults.

The findings come from a collaboration of researchers at Massachusetts General Hospital, Brigham and Women's Hospital, and Harvard Medical School, Boston; the University of Cambridge, England; and Paradigm Therapeutics, Cambridge, England. They appear in the Oct. 23 issue of The New England Journal of Medicine.

"It looks like we have found a key genetic gatekeeper of puberty in mice and men," researcher William Crowley Jr., MD, director of the Harvardwide Reproductive Endocrine Sciences Center, says in a news release.

An Unusual Saudi Family

Researcher Stephanie Seminara, MD, of the MGH reproductive endocrine unit, was looking for something else. Her team was trying to find the cause of a rare disease called idiopathic hypogonadotropic hypogonadism or IHH. Patients with IHH don't have any anatomical abnormalities but they do not go through puberty spontaneously and require hormones to help them reach puberty at the normal age.

Her search took her to Saudi Arabia. There she found a family in which many members -- both male and female -- never underwent puberty. Painstaking genetic analysis identified a mutant form of Gpr54 in family members with IHH, but not in those without the disease.

As it turns out, people with IHH only rarely have this particular abnormality in the mutant Gpr54 gene, but researchers turned up an African American male with different mutations in the same gene. That man never hit puberty.

Harry Potter to the Rescue

All this might have remained an interesting but unsolved puzzle, until a private company in England -- Paradigm Therapeutics -- learned that Seminara's team was studying Gpr54.

Paradigm was looking for new drug targets by creating mice that lack genes whose function is not yet known. Genetically engineered mice lacking these so-called orphan genes are called orphan mice. The Paradigm team names each strain of these mice after famous orphans. The Harry Potter strain, as it happened, lacked Gpr54.

Gpr54 isn't the only factor in the complex chain of events that leads to puberty. But puberty can't happen without it. The Harry Potter mice were normal in every way -- except that they never became sexually mature.

"These findings define a new drug target with wide potential for therapeutic intervention in conditions such as hormonal-dependant cancers, abnormal puberty, and control of fertility," Paradigm researcher Samuel Aparicio, PhD, says in a news release.