Signalling process for normal fertility located

Researchers at Otago and Heidelberg Universities have discovered how the brain circuitry vital to normal fertility in humans and other mammals operates. Their findings have been published in the international journal Nature Communications.

The researchers state that signalling between the small protein kisspeptin and its receptor, G-protein-coupled receptor 54 (Gpr54), is recognised as being essential for normal fertility, with Otago’s Professor Allan Herbison having also shown that the molecule is vital for ovulation to occur. “However,” they said, “the key cellular location of kisspeptin-Gpr54 signalling is unknown.”

Professor Herbison and his colleagues decided to assess the role of a small population of nerve cells in the brain called gonadotropin-releasing hormone (GnRH) neurons. They studied mutant mice which lacked Gpr54 receptors in only their GnRH neurons and found that these did not undergo puberty and were infertile. By inserting the Gpr54 gene into just the GnRH neurons, they were able to restore the mice back to normal fertility.

The researchers thus provide conclusive evidence that the GnRH neuron is the key site of kisspeptin-Gpr54 signalling for fertility. Professor Herbison said this discovery will help enable new forms of contraception and infertility treatments.

“It’s currently estimated that up to 20% 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,” he noted.

“Through detailing this mechanism, we now have a key chemical switch to which drugs can be precisely targeted.”

The researchers further 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.

The work was supported by the Health Research Council of New Zealand and the former Ministry of Science and Innovation. Professor Herbison said the findings represent a longstanding collaborative effort with the laboratory of Professor Gunther Schutz at Heidelberg University.

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