Strange animals have long piqued the interest of scientists. About 2,000 years ago, Aristotle and Pliny the Elder wondered at the unusual sex characteristics of the spotted hyena. Th ey noted the seemingly hermaphrodite genitalia of the females in addition to their larger size and general dominance over males. Th e reasons behind this “masculinization” of the female spotted hyena has perplexed scientists ever since. Th e creatures, which once roamed Europe, live in matriarchal clans in Sub-Saharan Africa and are the only mammals in existence in which the females lack an external vaginal opening. Instead, they urinate, copulate, and give birth through a pseudo-penis. No other species of hyena, of which there are four total in existence, has this bizarre genital apparatus.

Interested in solving the long-standing mystery of the “masculinization” of female spotted hyenas and uncovering other secrets of sexual development, Dr. Steve Glickman of the Field Station of the University of California, Berkeley, and colleagues brought the spotted hyena to their 29-acre lab. Th e Field Station operates under the philosophy that animals are best studied in an area that closely resembles their natural environment. Space is a rare and expensive luxury in laboratories, making the Field Station an unusual and valuable commodity for researchers working with exotic animals like the hyena.

Hyenas and Sex Hormones

Glickman called upon Dr. Geoffrey Hammond of the Child and Family Research Institute in Vancouver, British Columbia, to investigate how exposure to sex steroids may be responsible for the spotted hyena’s urogenital and social characteristics. Hammond suggested taking samples from all the hyena species to see how genetically similar they are. The team then compared sex-hormone binding globulin (SHBG) gene sequences, structures, and steroid-binding properties among the four types of hyena. They found that the spotted hyena has a very unique dilution of nine nucleotides that are responsible for coding proteins in a signal secretion polypeptide. The spotted hyena lacked three residues that were present in all other hyena species, thus producing abnormally low SHBG at five to 10 times less than the other species and causing the amounts of free androgen and free estrogen to be much elevated. The researchers concluded that this abnormality likely influences the masculinization of the female spotted hyena.

Hammond had never worked with hyenas prior to the experiment, but came away believing that the Field Station and Glickman’s work have much to contribute to the world of science, especially sexual development. “The hyena project is in some jeopardy due to the funding scenario, but is really important at this particular point in time,” he explains.

The 10,000 genomes project is sequencing the spotted hyena, and likely the oddwolf genome, which will open many doors for further research. Hammond anticipates the results of the sequencing to be available within a year.

“When we performed our genetic analysis, it was very clear to us that the identity at the genetic level between these four species of hyenas that look and behave very differently is almost the same as between us and chimpanzees. And yet it’s the only one that has this very strange phenotype. When we have these genome sequences available to us, we will be able to pinpoint the genetic differences between them.”

Tree Shrews and Sleep Research

The unique characteristics of exotic species off er some advantages for endocrinology research that regular lab rats and mice cannot replicate. In addition to the sex hormone scenario presented by the spotted hyena, tree shrews have proven to be an ideal candidate for neurobiology studies and other topics. These rodents are actually close relatives of primates and have the largest brain-tobody mass ratio of all mammals. They operate as a suitable, and much smaller, replacement for chimpanzees and other primates in a laboratory environment.

Dr. Eberhard Fuchs of the German Primate Center’s Clinical Neurobiology Laboratory and Professor at the Medical School of the University of Göttingen first came in contact with tree shrews while studying biology and sociology at the University of Munich.

“It was the time when the stress paradigm of tree shrews was being developed by Achim Raab,” he explains. “They were looking for mammals that demonstrated strong territorial behavior.” From these initial studies, researchers found that the tree shrew worked quite well for sociological and neurobiological studies. Now, Fuchs is publishing articles on the results of sleep disruption and other sleeprelated issues in tree shrews, which may off er insight into the same sleep factors for humans.

One key to the tree shrew’s importance, according to Fuchs, is its exclusively day-active nature. He describes the creature as “an excellent model for sleep research.” Many of his past studies have also focused on stress and depression because tree shrews can demonstrate symptoms very similar to that of a depressed person. By administering various antidepressants, he found that the animals respond quite well to certain medications. Other rodents are usually unsuitable for such research.

Although tree shrews take up more space than mice and are therefore more expensive, Fuchs says that the institute’s directors have been very supportive of his projects. The close genetic relationship to primates and comparatively small size make tree shrews a perfect compromise for such experiments. “They share very many similarities to primates, and an increasing number of studies are looking at the genetic similarities between humans and tree shrews. They have very well developed brains, and so for psychopathology studies in particular, they are ideal animals instead of mice or rats.” Other areas of study for tree shrews have included myopia and hepatitis.

Fuchs is currently seeking other locations in Europe that are interested in exploring research with these animals, but the appeal of the tree shrew has already extended its reach to Canada. Dr. Marc-André Lachance, a microbiologist from the University of Western Ontario, examined the Malaysian pen-tailed tree shrew’s special ability to metabolize massive amounts of alcohol. The animals live exclusively on fermented nectar that contains up to 3.8 percent alcohol.

Tree shrews with several times the legal limit of blood alcohol levels appear to have no signs of intoxication. Dr. Lachance hopes that this mystery, once solved, may introduce a better way to treat alcohol poisoning in humans.

While exotic animals are unlikely to become standard practice, innovative scientists may find great success by choosing a creature specially suited to their topic area. Working with a bone-crushing carnivore like the spotted hyena may present unique challenges but also unique benefits that can be found in no other animal. The obstacles of space and funding are ever present, but not insurmountable, as experts like Glickman and Fuchs have demonstrated. Additionally, Hammond is optimistic that the mapping of genomes will help unlock the secrets of animals like the spotted hyena. “We might even be able to explain a phenomenon that has been around since Aristotle described it in Ancient Greece,” he says.

—Mapes is a freelance writer in Washington, D.C., and a regular contributor to Endocrine News.

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