Hormone Healer

A new study about sexual attraction in mice is opening up the possibility of a new way to repair human brain damage.

Researchers found that when female mice responded to pheromones from dominant males, they produced new neurons in their brains, suggesting that hormone treatments may help damaged human brains by encouraging new growth. Several experimental drugs built around this idea are already in clinical trials and showing promising early results.

“Theoretically, the most important part of the study was that it revealed the pathway of how hormones triggered [the formation of] new neurons,” said Zhengui Xia, professor of environmental health at the University of Washington. Her review appeared along with the study in the August 2007 issue of Nature Neuroscience.

When a female mouse smelled the pheromones of an attractive male mouse, odor receptors in the female’s nasal cavity released two hormones: luteinizing hormone and prolactin. Those two hormones then stimulated neurogenesis, or the birth of new neurons, simultaneously in two parts of the female mouse’s brain: the hippocampus and the main olfactory bulb. There was no such reaction to submissive males.

The mating choices of female mice may also have resulted from neurogenesis. “We’ve found that these new neurons were required in forming female mice’s preference for dominant males,” said Chris Gregg, a postdoctoral fellow in molecular and cell biology at Harvard University who participated in the research as a Ph.D. candidate at the University of Calgary. When he and colleagues blocked neurogenesis during the study, the female mice appeared to have lost interest in both kinds of males.

Before the study, scientists already knew there were two places in the adult mammalian brain where new neurons were persistently generated. “But what they didn’t know was that they could happen simultaneously,” said Gregg. “Now we’ve proved that.”

Even though the study showed that female mice reacted strongly to pheromones exuded by dominant males, it’s still controversial as to whether humans can detect pheromones at all because the olfactory sense organs in our noses are much smaller in proportion than those in mice.

As pheromone usage in humans might sound far-fetched, researchers agreed that the most obvious medical application of the study lay in hormones. In fact, several pharmaceutical companies were already devising hormone therapies for stroke victims based on what has now been confirmed by the study. One of the therapies that is farthest along in development, called NTx-265, is a combination of two human hormones. One of them, called human chorionic gonadotropin, is similar in nature to the luteinizing hormone observed in the mice study.

Ongoing human clinical trials have demonstrated promising results. Each of the four patients who completed the 90-day study period has shown levels of recovery typically achieved by only 30 percent of stroke patients over the same amount of time.

Stem Cell Therapeutics, the Canadian biotech company that owns the new drug, said it was hoping to wrap up the drug’s preliminary trial on 11 stroke patients by the end of 2007. The complete data from human trials will not be released until next month.

When projecting applications of her research, Gloria Mak, lead author of the paper and Ph.D. candidate at the University of Calgary, said that it would be logical to develop drugs using luteinizing hormone. In fact, her supervisor, Samuel Weiss, was a scientific advisor to Stem Cell Therapeutics. However, the study itself was financially independent of the company, which didn’t exist when the discovery was made.

“People are experimenting with almost all similar hormones,” said Mak. “So far the results look good.”

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