NZ research shows which neurons flip fertility master switch

Kisspeptin neurons can "flip the switch" of fertility. Photo / Getty

Kiwi scientists have uncovered another secret of a wonder-protein that's already been shown to play a hand in reproduction and early brain development.

World-leading research by scientists at Otago University's Centre for Neuroendocrinology has boosted our understanding of kisspeptin, a protein discovered by accident a decade ago and now regarded as the body's "microchip" of fertility.

Following a landmark 2013 study that revealed the cell in our brain where the cascading process which results in fertility is triggered, Otago scientists have just demonstrated how kisspeptin neurons can "flip the switch" of our fertility master controller.

The findings, published this week in the prestigious journal Proceedings of the National Academy of Sciences (PNAS), provide the first direct evidence that these neurons work together to generate the small, episodic hormone pulses that are crucial to normal reproductive functioning in humans and other mammals.

The research could help future efforts to develop new fertility treatments, study leader Professor Allan Herbison said.

The pulses of the gonadotropin-releasing hormone (GnRH) to the pea-sized pituitary gland in the base of the brain have long been known to be essential to maintain fertility - but less clear has been the underlying mechanism that generates these pulses.

The pulses, which occur roughly every hour or so, prompt the pituitary gland to release two key hormones - LH and FSH - into the bloodstream, and also in a "pulsatile" manner, Professor Herbison said.

"Many types of infertility result from disorders of pulsatile hormone release, ranging from problems at puberty through to the inability to conceive," he said.

"For example, a very common cause of infertility in women, polycystic ovarian syndrome, is caused when pulses occur too fast."

A key unresolved question had been whether it was solely the GnRH neurons generating the pulse, or other activity in a wider network of neurons governing fertility.

To solve the riddle, Professor Herbison and his team used mice and state-of-the-art optogenetic techniques to selectively activate kisspeptin neurons in a particular part of the brain's hypothalamus.

After measuring blood samples, they found that activating this small population of kisspeptin neurons was remarkably potent at generating pulses of LH secretion.

When the researchers activated the kisspeptin neurons in mice lacking kisspeptin receptors on their GnRH neurons, no LH pulses were generated.

"These findings represent an important insight that will inform future efforts to develop new fertility treatments aimed at producing more or fewer GnRH pulses, depending on the problem."

It is thought that up to one-third of all cases of infertility in women involve disorders in the area of brain circuitry that Professor Herbison and his team are studying.

The research was supported by grants from the Health Research Council of New Zealand and the Marsden Fund.

Sealed with a Kiss

•The accidental discovery of kisspeptin - a protein which in humans triggers a cascade of biochemical changes that lead to fertility and puberty - proved a major leap in understanding how our body works.
•The same team of Otago University researchers who helped to establish the cell in the brain where kisspeptin activated the sequence of events that enabled fertility have since shown how it plays a key role in moulding the male brain just hours after birth.
•Their latest study, published this week, has now demonstrated how kisspeptin neurons can "flip the switch" of our fertility master controller.
•The protein, encoded by the KISS1 gene in humans, was originally named after the Hershey Kiss chocolate by US researchers based in Hershey, Pennsylvania. At the time they had no idea that it had a role in fertility.