Final piece found in puzzle of brain circuitry controlling fertility

September 20, 2013, University of Otago

In a landmark discovery, the final piece in the puzzle of understanding how the brain circuitry vital to normal fertility in humans and other mammals operates has been put together by researchers at New Zealand's University of Otago.

Their new findings, which appear in the leading international journal Nature Communications, will be critical to enabling the design of novel therapies for as well as new forms of contraception.

The research team, led by Otago neuroscientist Professor Allan Herbison, have discovered the key cellular location of signalling between a small protein known as kisspeptin* and its receptor, called Gpr54. Kisspeptin had earlier been found to be crucial for fertility in humans, and in a subsequent major breakthrough Professor Herbison showed that this molecule was also vital for ovulation to occur.

In the latest research, Professor Herbison and colleagues at Otago and Heidelberg University, Germany, provide conclusive evidence that the kisspeptin-Gpr54 signalling occurs in a small population of in the brain called gonadotropin-releasing hormone (GnRH) neurons.

Using state-of-the-art techniques, the researchers studied mice that lacked Gpr54 receptors in only their GnRH neurons and found that these did not undergo puberty and were infertile. They then showed that infertile mice could be rescued back to completely normal fertility by inserting the Gpr54 gene into just the GnRH neurons.

Professor Herbison says the findings represent a substantial step forward in enabling new treatments for infertility and new classes of contraceptives to be developed.

"Infertility is a major issue affecting millions of people worldwide. It's currently estimated that up to 20 per cent of New Zealand couples are infertile, and it is thought that up to one-third of all cases of infertility in women involve disorders in the area of we are studying.

"Our new understanding of the exact mechanism by which kisspeptin acts as a master controller of reproduction is an exciting breakthrough which opens up avenues for tackling what is often a very heart-breaking health issue. Through detailing this mechanism we now have a key chemical switch to which drugs can be precisely targeted," Professor Herbison says.

As well as the findings' benefits for advancing new therapies for infertility and approaches to controlling fertility, they suggest that targeting kisspeptin may be valuable in treating diseases such as prostate cancer that are influenced by sex steroid hormone levels in the blood, he says.

Professor Herbison noted that the research findings represent a long-standing collaborative effort with the laboratory of Professor Gunther Schutz at Heidelberg University, Germany.

Professor Herbison is Director of the University's Centre for Neuroendocrinology, which is the world-leading research centre investigating how the brain controls fertility.

"We are delighted to have published this work in one of the top scientific journals and also to be able to maintain the leading role of New Zealand researchers in understanding fertility control," he says.

Explore further: Fertility and weight relationship investigated

More information: *Kisspeptin 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.

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JVK
1 / 5 (9) Sep 21, 2013
Is anyone else surprised to see that the link is to GnRH, which some people have called THE biological core of mammalian reproduction? Herbison and others have already shown that its pulsatile secretion is nutrient (i.e., glucose and amino-acid)-dependent, and I have detailed that GnRH pulsatile secretion is pheromone-controlled in model of adaptive evolution in species from microbes (e.g., yeasts) to man. The conserved molecular mechanisms and fixation of new alleles clearly refute any aspect of mutation-driven evolution via incorporation of cellular level theromodynamic stability required for adaptively evolved organism-level thermoregulation in unicellular and multicellular organisms. See for examples: Nutrient-dependent/pheromone-controlled adaptive evolution: a model http://www.socioa...ew/20553 Is there any need for biologists/physiologists to apologize to evolutionary theorists for making them look foolish?
Captain Stumpy
1 / 5 (7) Sep 22, 2013
"Infertility is a major issue affecting millions of people worldwide. It's currently estimated that up to 20 per cent of New Zealand couples are infertile, and it is thought that up to one-third of all cases of infertility in women involve disorders in the area of brain circuitry we are studying. "


is it just me or does that seem abnormally high for an area? i know it says estimated, but that is still very high! 1 in 5!

could there be an exposure issue? another cause that affects the kisspeptin-Gpr54 signaling? just thinking out loud...
JVK
1 / 5 (3) Sep 23, 2013
Nutrient-stress and social-stress that contribute to altered GnRH pulse frequency are sources of physical diseases and mental disorders in all human populations worldwide. If not for the statistical approach to population genetics based solely on ideas like those proposed by Haldane more than 80 years ago, and uncritically adopted by evolutionary theorists, we would already have cures for many more stress-related illnesses.

The refutation of mutation-driven evolution, was published in this same journal on 9/13/13, and even in the light of what's been confirmed about how GnRH pulse frequency fixes new nutrient-dependent alleles, when alleles associated with mutations are not fixed (http://www.nature...7.html), the refutation of mutations theory in natural selection is being ignored.

It is amazing to see ignorance trump evidence when results of scientific experiments are published in the same journal that should eliminate the ignorance.

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