The cosmetics industry goes to mind-boggling lengths to cash in on human vanity; marketing glamorous fragrances designed to make us irresistibly attractive. But when it comes to getting serious about attracting a mate, some of the least alluring species have it made; the pig pheromone, androstenone,can make even the ugliest old boar attractive to an eligible female. In fact,many species regulate their fertility through pheromones, but how do these strong chemical messages translate quickly into hormonal responses? Kennedy Wekesa has spent most of his career teasing apart the complex signalling cascades that are triggered when an animal picks up a hint of pheromone. Knowing that young female mice sense pheromones with receptors on the surface of the tiny vomeronasal organ, Wekesa has turned his attention to the effect pheromones have on the sensory organ at the cellular level and found the sex signal's transduction proteins ().
Most female mice naturally go through puberty at about 28 days old, but introduce a male to the litter, and the young females' sexual development is accelerated. Wekesa already knew that he could prevent the pronounced effect that the males have on young females by removing the youngster's pheromone-sensitive vomeronasal organ, so he decided to test how sensory cells on the surface of young female's vomeronasal organ transform the pheromone's external chemical signal into a physiological response.
Most cells respond to external events through a cascade of cellular events that are triggered when a chemical signal binds to a receptor buried in the cell's membrane. The receptor activates a G protein by changing it's structure so that it binds GTP and, in turn, activates a third enzyme, which then releases a soluble signalling molecule such as inositol 1,4,5-trisphosphate(IP3) from its membrane tether, to diffuse through the cell to trigger the next stage of signal transduction. Wekesa knew that female pigs produce the IP3 signal when they are dosed with their male's pheromones, but would female mice respond in the same way? Before he could begin teasing apart the signalling cascade, Wekesa needed to collect male pheromones; he needed fresh male mouse urine every day!
Wekesa began the tricky task of dissecting out the tiny sensory organs from the young female's nostrils, ready to test the urine's effect on the sensory cells. Sure enough, after treating the sensory cell's membranes with male urine, the sensory cells triggered production of the IP3 cellular signal. But which G protein was the intermediary between the receptor and the IP3 signal? Wekesa began using a variety of blocking agents that specifically targeted the three different G proteins that he knew triggered IP3 release and finally determined the crucial G protein that stands between the males and their female's response; Gq/11.
Having identified the proteins that transmit the male's potent message,Wekesa is keen to translate the message itself. He hopes that by identifying the pheromone compounds that the females respond to, he might be able to turn the pheromones against the mouse population in an effort to control their record fecundity.
