Puberty is a puzzle for teenagers and researchers alike. Although scientists can explain part of the process that turns children into adults, no one knows exactly what triggers it. Now a team has identified a hormone that helps tell the brain when "it's time!" The find could have broader implications for fertility treatments, contraceptives, and even fighting cancer.
It's no secret that teenagers have raging hormones. At puberty's onset, the body releases pulses of gonadotropin-releasing hormone (GnRH), which unleashes a flood of sex hormones such as estrogen and testosterone in the ovaries and testes, respectively. That, in turn, triggers the outward signs of puberty, such as breast growth and menstruation in girls and facial hair, muscle development, and sperm production in boys.
But what sets off neurons in the brain that control the release of GnRH? The romantically named protein kisspeptin seems to be one trigger. When kisspeptin is given to young monkeys, it can spark puberty (ScienceNOW, 1 February 2005). (Maturing monkeys undergo the same sorts of changes that human teenagers go through.) But scientists strongly suspected that the protein was not acting alone.
Now studies of several families in Turkey with members who failed to undergo puberty have identified another important molecular player. Ali Kemal Topaloğlu of Çukurova University in Balcali, Turkey, and his colleagues collected blood samples from nine families with multiple members suffering from so-called idiopathic hypogonadatropic hypogonadism, for whom puberty never starts. The girls never menstruate, and the boys don't grow facial hair, remain short, and have undeveloped sex organs. In three of the families, the researchers found a mutation in the gene that codes for a receptor for Neurokinin B, a hormone found in several areas of the brain and whose function had been unclear. In a fourth, they found a mutation in the gene that codes for the hormone itself. Based on the mutations' effects, a signal from the hormone seems to be a key trigger of puberty, the researchers report online today in Nature Genetics.
The hormone and its receptor are a potentially promising therapeutic target for conditions involving sex hormones, says co-author Robert Semple of the University of Cambridge in the United Kingdom. The receptor is a member of a family of proteins called G protein-coupled receptors, which researchers have found fairly easy to target with drugs. Such therapies might be useful in treating either early or late puberty, which can have serious social consequences for the teens affected. (Girls who enter puberty early, for example, are at much higher risk for substance abuse and teen pregnancy.) Compounds targeting the receptor might also function as contraceptives or fertility drugs by either shutting down or ramping up the production of fertility-regulating hormones. The receptor could also be a target of therapies for breast or prostate cancer, because those tumors depend on sex hormones for their growth.
But before that happens, scientists need to figure out exactly what Neurokinin B and its receptor are doing, says pediatric endocrinologist Nicolas De Roux of INSERM's Laboratory of Hormone Studies in Paris, who notes that the find is exciting and "very surprising." Scientists knew that the hormone was expressed in the brain regions involved in triggering puberty--and that it is expressed differently in males and females--but whether the hormone is a direct "on" switch or plays a more subtle role is not yet clear, he says. "There's a lot of work left to do."
