Kisspeptin -- the wonder protein recently revealed as a master controller in reproduction -- has now been found by New Zealand researchers to play a key role in moulding the male brain just hours after birth.
In a landmark study last year, kisspeptin -- originally named after the Hershey Kiss chocolate by US cancer researchers based in Hershey, Pennsylvania -- was revealed to trigger a cascade of biochemical changes in the body that lead to fertility and puberty.
The same Otago University researchers behind that breakthrough have now found kisspeptin is critical to making newborns' brains function as male.
Professor Allan Herbison, who led the team, said the findings reveal that kisspeptin, which has only been discovered to play any role in fertility in the past decade or so, is a much more remarkable molecule than previously thought.
"Not only does kisspeptin signalling act as a master switch for puberty and ovulation, we now show how in the first hours of drawing breath it also triggers our brains to develop differently according to our sex."
Their recent investigtation, published today in the Journal of Science, showed that male-specific signalling in the Gona dotropin-releasing hormone (GnRH) neurons of new-born mice was crucial to generating a testosterone surge that occured up to five hours after birth.
This brief but powerful increase in testosterone blood levels, which only takes place in males, is known to cause their brains to develop differently to females.
Among other effects, these brain differences are implicated in the patterns of neurological disorders that men and women suffer.
Professor Herbison said sex differences in brain function were established during the later stages of foetal development and around birth -- but the actual cellular mechanisms underlying these important actions remained unknown.
Through a series of investigations in mice, he and his colleagues have now shown that a small group of GnRH neurons in the brain's hypothalamus become active only in new-born males, and not females.
Additionally, they found that a small population of kisspeptin neurons appeared at this time, once again only in males.
In their latest investigations, the researchers also show that male mice lacking kisspeptin receptors on their GnRH neurons do not experience the usual testosterone surge following birth.
They also determined that, as adult males, such mice had female-like brain characteristics.
The findings published last year were a large leap toward better understanding kisspeptin, and put researchers on the path to trying to enable fertility in women who are infertile and get ovulation.
It is estimated up to 20 per cent of New Zealand couples are infertile, and about one-third of all cases of infertility in women involve disorders in the area of brain signalling to the ovaries.
The new study was undertaken by Professor Herbison and Dr Jenny Clarkson of the Centre for Neuroendocrinology and Department of Physiology in collaboration with researchers in Canada and Germany.
The work was supported by the Health Research Council of New Zealand and the former Ministry of Science and Innovation.
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Kisspeptin: the microchip of fertility
*The accidental discovery of kisspeptin a decade ago proved a major leap in understanding how our body works. At the time of its discovery 10 years ago, scientists had no idea of the crucial role it plays.
*The protein, encoded by the KISS1 gene in humans, triggers a cascade of biochemical changes that lead to fertility and puberty.
*Otago University researchers helped to establish the cell in the brain where kisspeptin activates a sequence of events that enables fertility.
*In a study published today, they have also determined it binds to specific nerves and kick-starts a brief but powerful testosterone surge in male babies within five hours of birth, causing their brains to develop differently from females.
*Scientists have suggested other important medical applications, namely using it to block production of hormones that nurture tumours in breast and prostate cancers.
By Jamie Morton of the New Zealand Herald