The Secret Ingredient in Eau De Goat

Sometimes, for science, you have to make fashion accessories for animals. I’ve written about swift backpacks, cheetah collars, and beetle mittens. Now, from Ken Murata from the University of Tokyo, comes the goat cap. It’s a custom-made helmet with a few gas-absorbing balls inside. Its purpose is to collect a dose of ‘eau de goat’, so the team could identify the secret ingredients that allow male goats to turn females on.

If you have a herd of female goats or sheep, you can quickly shunt them into the fertile part of their sexual cycles by introducing a male. Something in his scent triggers hormonal changes in the females, who start to ovulate, or produce egg cells.

This “male effect” was discovered decades ago, but no one knew which molecules were responsible. They seemed to be classic examples of ‘primer pheromones’, which work by triggering long-lasting physical changes in their targets, rather than suddenly changing their behaviour.

To identify these mystery pheromones, Murata’s team analysed the odour samples collected by their gas-absorbing caps. Specifically, they were looking for chemicals that were released by normal males but not by castrated ones that don’t induce the male effect. They ended up with a long list of candidates. Now they had to test them.

They knew that the male pheromones act on a particular group of neurons in the female’s brain, which release a hormone called GnRH. This “GnRH pulse generator” works like clockwork, releasing a fresh burst of GnRH every 27 minutes or so. The size and frequency of these pulses dictates a female’s reproductive cycle. For example, she produces an especially large surge of the hormone just before her most fertile phase.

The neurons produce a volley of coordinated electrical activity whenever they released a hormone pulse, and Murata could detect these bursts by sticking electrodes in the right place. He could then waft different scents past their noses to see how the pulse generator responded.

When he held a cup full of male hair up to the female’s noses, their GnRH neurons produced a volley of activity, no matter where they were in their 27-minute cycle. A cocktail of 18 newly identified compounds from the male goats also worked. And eventually, the team found that a single chemical called 4-ethyloctanal did the trick. It seems to be the key ingredient behind the male effect.

4-ethyoctanal has a citrus tang, but it’s one easy chemical reaction away from a substance responsible for a goat’s distinctive “goaty odour”. This is the first time anyone has found the substance in a natural source, and it just so happens that it’s a primer pheromone.

Peter Brennan from the University of Bristol says the discovery is important. “There are relatively few instances in mammals where an individual compound has been positively identified as having a pheromonal effect,” he says. “There are fewer still in non-rodent species that have commercial importance.”

After more work, farmers may be able to use 4-ethyloctanal to more precisely control the reproduction of their herds. And Murata’s group have assembled an even bigger team to find a similar pheromone in an even more commercially important animal—the cow.

“I would expect that what they find in the goat will be true for other mammals and can be more easily studied in more traditional scientific models such as the mouse,” says Lisa Stowers from the Scripps Research Institute notes. But she says that “this finding is unlikely to translate to human reproduction”, since we don’t seem to have any pheromone-detecting neurons similar to the ones that Murata studied in his goats.

There are still some missing pieces to the puzzle, though. Tristram Wyatt form the University of Oxford adds that “4-ethyloctanal is likely to be one of a number of molecules working synergistically.” After all, Murata’s team showed that their 18-molecule cocktail still partly affected the females even when 4-ethyloctanal was removed.

And other stimuli could potentially block the pheromone’s effects—something we still know little about. “In more natural situations, the male effect in sheep (and likely goats) comes especially from exposure to unfamiliar males,” says Wyatt. “So, there is also memory of individual chemical profiles of previously encountered males which blocks the effect of pheromone.”

Stowers adds that the team haven’t shown how the pheromone actually affects the GnRH neurons or how a brief sniff can lead to long-lasting changes over the course of several days. Yukari Takeuchi, one of the study’s leaders, agrees. He says the acid test for their hypothesis would be to expose females to synthetic 4-ethyloctanal and to watch their reproductive behaviour change in the absence of any actual males. To do that, they need to create a device that will continually release the pheromone, and they are building one right now. Their days of goat accessories aren’t over yet.

Reference: Murata, Tamogami, Itou, Ohkubo, Wakabayashi, Watanabe, Okamura, Takeuchi & Mori. 2014. Identification of an Olfactory Signal Molecule that Activates the Central Regulator of Reproduction in Goats.

Current Biology http://dx.doi.org/10.1016/j.cub.2014.01.073