Research collaboration identifies gene essential to puberty

One of the great mysteries of human biology is what controls the timing and onset of puberty. By studying patients who fail to undergo puberty and using information made available by the Human Genome Project, American and British research teams have collaborated to identify a gene that appears to be a key regulator of puberty in humans and in mice.

In a report published in the October 23 New England Journal of Medicine, scientists from Massachusetts General Hospital (MGH) and from Paradigm Therapeutics and the University of Cambridge in the U.K. describe mutations in the gene for a protein called GPR54 that prevent both humans and mice from undergoing normal puberty and sexual maturation. This gene makes a receptor protein that probably is a key trigger of the hormonal cascade required for mammalian reproduction. The discovery could lead to new infertility treatments or contraceptive options, among other applications.

"It looks like we have found a key genetic gatekeeper of puberty in mice and men," says William Crowley Jr., MD, chief of the MGH Reproductive Endocrine Unit and director of the Harvardwide Reproductive Endocrine Sciences Center, one of three co-senior authors of the NEJM report. "Most other genes involved in reproductive control are species-specific, but this gene shows robust activity across two very different mammalian species."

The MGH effort led by Stephanie Seminara, MD, of the Reproductive Endocrine Unit began as a search for genes that cause idiopathic hypogonadotropic hypogonadism (IHH), a relatively unusual disorder in which puberty does not occur at the usual age. Normal puberty begins when the hypothalamus, a structure deep within the brain, begins to secrete gonadotropin-releasing hormone (GnRH). In response to this secretion, the pituitary gland releases hormones called gonadotropins, which in turn stimulate the ovaries or testes to start releasing estrogen and testosterone. Individuals with IHH fail to

Contact: Sue McGreevey
Massachusetts General Hospital

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