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Puberty Starts With a 'KiSS'

Gene awakens reproductive system at right time, researchers report

MONDAY, Jan. 31, 2005 (HealthDayNews) -- When it's time for boys and girls to enter that daunting stage of life known as puberty, their reproductive systems are first awakened with a kiss, namely the KiSS-1 gene.

At the right time, this gene sends out a molecular signal that activates a receptor in another gene called GPR54, and puberty is the end result, researchers report in this week's online issue of the Proceedings of the National Academy of Sciences.

"Ovarian and testicular function is absolutely dependent on the secretion of pituitary hormones," said study author Tony Plant, director of the Center for Research in Reproductive Physiology at the University of Pittsburgh School of Medicine. "In turn, pituitary function is absolutely dependent on a brain hormone called gonadotropin-releasing hormone (GnRH), which is critical for normal reproduction."

According to Plant, this genetic signaling system is active in the fetus during late pregnancy and in early infancy. Then, this hormone is turned off. "It's basically put to sleep for 10 years and then turned back on. How this happens is really a mystery," he said.

In humans, it had been shown that those with a mutation of the GPR54 gene do not enter puberty and cannot sexually reproduce.

Using that information, Plant's team, in experiments with monkeys, found a signaling system in the hypothalamus of the brain that involves both GPR54 and the KiSS-1 gene that appears necessary to restart the reproductive system.

In addition, the researchers found that by giving monkeys kisspeptin, which is the substance secreted by the KiSS-1 gene, before puberty, they were able to wake up the reproductive hormones. In fact, within 30 minutes of giving kisspeptin to male monkeys, levels of one of the dormant hormones increased dramatically once it was stimulated by GnRH.

Plant believes it is possible there is a clock in the brain that tells these genes to wake everything up. "Or instead of a clock in the brain, there is something that tracks growth, and when the adult size is reached, it tells the reproductive axis that the right size for reproduction has been reached," he said.

In future experiments, the researchers hope to see if giving kisspeptin can turn on the full reproductive system at will, Plant said.

"Previously, we had known the gene that triggers puberty, and now we are one step closer to the control of this system by identifying this receptor and this signaling system," Plant said. "I think we now have a better understanding of the triggering mechanism in the brain."

According to another study author, this discovery could have clinical applications. "This system could be important in stimulation of the reproductive axis in some cases," said Dr. Stephanie B. Seminara, an assistant professor of medicine at Harvard Medical School. In other clinical situations, it could also be important by suppressing the reproductive axis, she added.

"There are many common clinical conditions, such as infertility or certain types of hormone-dependent cancers where standard therapy involves suppressing the reproductive cascade," Seminara explained. "The discovery of this peptide and its receptor is another key regulatory gate for the whole system, and may lead to drugs that can be used to regulate the reproductive axis."

"This is likely to be an important protein in puberty," said Dr. Lawrence Layman, a professor of obstetrics and gynecology at the Medical College of Georgia.

"But, there must be five or ten genes that if there's a mutation make puberty absent," he added.

Layman said that he has seen only two patients who have a fertility problem that is due to mutations in these particular genes.

"It's an interesting and important finding. It's something that helps tell us about puberty" he said. "But I doubt it's the only thing."

More information

The National Institutes of Health can tell you more about puberty.

SOURCES: Tony Plant, Ph.D., professor, cell biology, and director, Center for Research in Reproductive Physiology, University of Pittsburgh School of Medicine; Stephanie B. Seminara, M.D., assistant professor, medicine, Harvard Medical School, Boston; Lawrence Layman, M.D., professor obstetrics and gynecology, Medical College of Georgia, Augusta; Jan. 31-Feb. 5, 2005, Proceedings of the National Academy of Sciences online
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