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The biology behind the raging-hormone rite of passage known as puberty has long been a mystery. Just as the pimply, mood-swinging teen puzzles parents, the process that sets the teenager off has also stumped scientists.

But researchers from Turkey and England say they have discovered one of the master molecules that triggers sexual maturity.

Their work is based on the study of four Turkish families whose children, sexually speaking, will never grow up.

By hunting for the genetic flaws behind this rare condition, scientists identified two genes involved in the production of a crucial hormone in the brain that cues the body to bud.

The finding, which appeared yesterday in an advance online edition of Nature Genetics, could lead to new treatments for a range of conditions that involve sex hormones - from early puberty to infertility, to breast and prostate cancers.

"These rare people have given us insight into normal processes," said co-author Robert Semple, a clinician scientist at the University of Cambridge.

While Dr. Semple acknowledged the results must now be confirmed in larger populations, he said the hormone "could be the master switch."

"There will be huge interest that will explode around the world," he predicted. "People with patients will screen their genes [for these mutations]."

Cheri Deal, a pediatric endocrinologist at the University of Montreal, agreed that the finding will help to detect affected children "well before they get to puberty…instead of waiting until they end up on our doorstep at 15 or 16, when there's already been psychological damage."

Lead author Kemal Topaloglu, a pediatric endocrinologist at Cukurova University in Adana, Turkey, worked with the Cambridge group after years of caring for children who never hit puberty. Research suggests that the genetic condition, known as hypogonadotropic hypogonadism (or HH for short) strikes roughly one in 1,000 males, and fewer than one in 5,000 females.

But Dr. Topaloglu explained in an interview this week that the incidence is higher in Turkey where close relatives have often intermarried.

Researchers found that eight children from four families in the study were afflicted after inheriting two copies of a faulty gene - one from each parent.

Ranging in age from five to their mid-20s, the offspring were born with sexual equipment that could not develop naturally, leaving them sexually immature and infertile.

"It is quite stressful for these patients, psychologically," Dr. Topaloglu said, "for the girls to have no breast tissue when they are with their peers or for the boys who see everyone else shaving and their voices changing."

Hormone-replacement therapies can help with these outward signs of sexual maturity, but restoring fertility tends to be more complicated, the doctors said.

In all, researchers scanned the DNA of nine Turkish families affected with HH and found the common genetic mutations in four of them.

The afflicted family members carry versions of two genes, either TAC3 or TACR3, that do not function.

Both genes are ancient, Dr. Semple said, hearkening back to our reptilian past - suggesting they're crucial to the survival of our species.

TAC3 makes Neurokinin B, a hormone best known to play a role in blood vessels and the gut. But it has also been implicated in pregnancy and menopause.

The other gene, TACR3, makes the brain receptors that sit on the surface of cells to which Neurokinin B binds.

Neurokinin B sparks the brain's hypothalamus region to unleash the chemical cascade that underlies puberty.

This part of the endocrine system actually first sparks to life in the womb. It sends signals from brain to body that orchestrate the construction of ovaries or testes.

But after a child is born, the system slips into a state of dormancy until puberty. At that tumultuous time, the brain produces so-called gonadotropin-releasing hormones that signal the pituitary gland to pump other hormones into the bloodstream. This prompts the sex organs to action.

In females, the ovaries secrete estrogen and progesterone, which in turn widen hips, enlarge breasts, trigger hair growth and the onset of menstruation.

In males, the testes make androgens and testosterone, which deepen the voice, enlarge bones and muscles, spur hair growth and the production of sperm.

Precisely what flicks that switch to sexual maturity has been "an enduring enigma of human biology," the researchers wrote in their paper.

But since the Turkish subjects who failed to enter puberty lacked Neurokinin B, they suspect this hormone represents at least one of the major switches.

"Neurokinin is the hormone that signals the hypothalamus to signal the pituitary gland," Dr. Topaloglu said.

Receptors for Neurokinin B can be found throughout the brain and researchers said it is unclear how the lack of this hormone affects mental abilities. Two girls in the study unable to make Neurokinin B because of mutations in TAC3 suffered mental delays.

But Dr. Topaloglu noted that other subjects with mutations in the TACR3 receptor gene are on the honour roll at school.

TAC3 and Neurokinin B are not the first molecules to be linked to the onset of puberty. In 2003, researchers from the United States and Britain found members of a Saudi Arabian family who suffered from HH carried mutations in a gene called GPR54. Mutated, this gene also blocked sexual maturity in mice and it was billed as a key trigger of puberty.

But none of the children who failed to reach puberty in the nine Turkish families studied carried mutations in the GPR54 gene. As well, five of the Turkish families do not carry mutations in the new genes identified.

Dr. Topaloglu said this is evidence that there are likely to be several genes involved in sparking puberty.

"I don't think there's only one player to explain this complex system," he said. "There's probably 20."

Dr. Semple's group is now studying the function of Neurokinin B in mice and Dr. Topaloglu continues to study his patients for other genes to explain their failure to reach puberty.

Dr. Deal, who is also president-elect of the Canadian Society of Endocrinologists and Metabolism, noted that some of the candidate genes involved in puberty are linked to the olfactory system. This would explain why some who suffer from HH can lack the sense of smell.

"We're still barely into the water if you look at it like an iceberg," she said.