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A gene's first 'kiss' sets off that affair known as puberty

builds on the discovery made independently by both Harvard and French researchers that a gene called GPR54 is defective in children with a rare disorder that inhibits puberty's onset. To better understand what role GPR54 plays in the initiation of puberty, as well as learn about KiSS-1, which in earlier rodent studies had been identified as a molecule that activates a signal receptor of GPR54, the researchers looked to the nonhuman primate, the only animal with a reproductive system in common with the human's.

The onset of puberty becomes official when gonadotropin-releasing hormone (GnRH) is secreted and sets off a chain reaction of chemical messages. Inside the hypothalamus, nerve cells release GnRH in a 'round-the-clock,' pulsatile fashion. With each secretion, the pituitary gland is stimulated to secrete its own messengers, lutenizing hormone (LH) and follicle-stimulating hormone (FSH), directly into the circulation. In turn, these rising levels of LH and FSH cause the testes and ovaries to produce the sex hormones testosterone and estradiol, the culprits responsible for the physical changes and emotional baggage of male and female puberty, respectively.

"We now have very good evidence that the GPR54 gene and its switch, the kisspeptin protein molecule produced by KiSS-1, are key to the initiation of puberty, when GnRH is released," Dr. Plant said. "However, it's unlikely that they act alone. Other signaling systems, some of which have probably yet to be identified in humans, help control GnRH release in primates."

Besides learning that GPR54 and KiSS-1 are expressed inside the hypothalamus of primates at the time of puberty, the researchers also found that by giving animals kisspeptin they could, essentially wake up the reproductive hormones from their childhood hibernation. Within 30 minutes of kisspeptin being administered to male monkeys, LH, one of the hormones stimulated by GnRH secretion, was no longer dormant, with levels 25-times
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Source:University of Pittsburgh Medical Center


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