What can urine tell us?

Image credit: Flickr user Knowtex.

My urine has been tested for many things. For example, when I was offered my current job, my urine was tested for the presence of metabolites of illegal drugs. Drug metabolites are the breakdown products of various drugs, which remain in your blood until they are cleared by your liver or kidney and excreted in the urine. Because they stay in the body longer than the active drug, the window of detection is longer.

Last summer I had some liver problems, and my urine was detected for the presence of a whole host of different things that could give my doctors insight into my condition. It was tested for white blood cells, which are part of the immune system, and bilirubin, which is a by-product of the breakdown of red blood cells in the liver. An abnormally high concentration of either of these in my urine could indicate an infection or a hyperactive liver.

I’ve taken pregnancy tests that test my urine for the presence of an endocrine called human chorionic gonadotropin, or hCG. This endocrine is produced by the developing placenta of an embryo that has recently implanted in the uterine wall. This endocrine communicates with the corpus luteum, which is the now-empty follicle in the ovary from which the egg was released, telling it to continue to release another endocrine called progesterone. Progesterone is needed for the maintenance of the uterine wall during the pregnancy. Without the influence of hCG, the corpus luteum would die, eventually causing the woman to have her period. In my case, fortunately, my urine has always come back negative for levels of hCG that would indicate an implanted embryo. (I say fortunately because, trust me, I ain’t ready.)

My urine has been tested for the presence of a number of things throughout my life, all in the interest of medical, personal, or professional discourse. But humans are not alone in the venture of inspecting urine to learn more about themselves or others. Most people are familiar with the concept of pheromones, which are chemicals released as intraspecies messengers to elicit a social response. For example, the stinky urine that tomcats spray around their territory carries volatile compounds that send a clear message to other cats: This is mine. Stay away. The release of pheromones is to provide a benefit to the releaser and usually the receiver as well. When the tomcat sprays pheromone-laden urine, he benefits because it keeps away interlopers, and the potential interlopers benefit because they get to avoid a fight.

Tomcats use pheromones their urine to send messages intentionally, but sometimes the compounds in an animal’s urine can send unintentional messages. Arecent study in PNAS describes a compound in carnivore urine that helps prey species like mice and rats avoid predators. This compound, called 2-phenylethylamine (PEA), is something called a kairomone. Unlike pheromones, kairomones are interspecies messengers, allowing the receiver to ‘eavesdrop’ on the individual that left them behind. In the case of PEA, when rodents detect this kairomone, they know that a predator is in the area.

PEA triggers a rodent’s stress response and elicits avoidance behaviors that help the rodent escape predation by avoiding areas where there’s a lot of carnivore pee. Liberles and colleagues exposed rats to the urine of two different carnivores, isolated PEA, benzylamine (a chemical strongly related to PEA), and water. They found that the rats avoided the pure PEA and urine, but spent similar amounts of time around the water and benzylamine (see figure, adapted from the data in Liberles et al., 2011; click to enlarge), which suggests that rats show avoidance of PEA and can distinguish PEA from very similarly-related compounds. When PEA was enzymatically removed from lion urine, the rats no longer avoided it, spending similar amounts of time near the PEA-depleted urine as they spent near water. Similar experiments in mice show that the avoidance of PEA is dose-dependent, meaning that rodents will exhibit stronger avoidance behavior when the concentration of PEA is increased. Additionally, exposure to PEA provoked an increase in the circulating level of the rodent stress hormone corticosterone.

This is actually really cool because PEA is fairly ubiquitously present in the urine of carnivores and also relatively specific to carnivores as opposed to other mammalian species. As you can see in the chart (adapted from the data in Liberles et al., 2011; click to enlarge), many carnivore species have PEA concentrations in their urine that are an order of magnitude greater than those of rodents and other non-carnivore mammals. While rodents can also detect chemicals that are specific to the predator species that they encounter the most, their sensitivity to PEA allows them to recognize and avoid predator species that they have never even encountered before.

You might ask why carnivores have more PEA in their urine than other mammals do, but the answer isn’t clear at this time. There are a couple of possibilities, and the answer is likely a combination of the two. PEA is a metabolite of one essential amino acid found in dietary protein, so it may be that the sheer volume of protein in the diet is a contributing factor. It is also likely that carnivores have shared metabolic pathways that specifically produce PEA over other possible metabolites. Another possibility is that PEA might be produced in high concentrations to act as a pheromone in some carnivore species, and rodents adapted the ability to listen in on this pheromone as a kairomone.

Originally posted at Scientific American on July 25, 2011.

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Ferrero, D., Lemon, J., Fluegge, D., Pashkovski, S., Korzan, W., Datta, S., Spehr, M., Fendt, M., & Liberles, S. (2011). Detection and avoidance of a carnivore odor by prey. Proceedings of the National Academy of Sciences, 108 (27), 11235-11240 DOI: 10.1073/pnas.1103317108