In order to protect males with low-testosterone from the effects of anxiety and depression, much of the testosterone in his brain must first be converted into estrogen, according to new findings by a researcher at Florida State University College of Medicine.

Mohamed Kabbaj, a professor of biomedical sciences received a six-year grant from the National Institute of Mental Health to investigate the ways in which anxiety affects the sexes differently.

Kabbaj already knew that testosterone tends to protect males from depression and anxiety, just as estrogen and progesterone do in females. He also knew that most testosterone was converted into estrogen in the brain. What he didn’t know, however, was that those anxiety- and depression-inhibiting actions couldn’t take effect until the testosterone was first converted to estrogen.

“There is an enzyme in the brain that ‘mediates’ the conversion of testosterone into estrogen,” Kabbaj said. “We inhibited that enzyme in a specific brain area implicated in the regulation of mood. And when you do that, you lose the antidepressant effect of testosterone. So the conversion is very important.”

His research targeted the hippocampus area of the brain, where testosterone acts through what’s known as the MAPK pathway to deliver its antidepressant and anti-anxiety effects.

“But we have to be careful about that pathway,” Kabbaj said, “because it’s also implicated in cellular growth and cancer. Therefore, we’re looking for other pathways that don’t have these effects. It’s complicated. Nothing is ever simple, but we’ll get there.”

Women are 70 percent more likely than men to suffer from depression during their lifetime, according to National Institute of Mental Health. So far, the link between testosterone conversion and anxiety/depression has been detected only in laboratory animals. But Kabbaj says the results are potentially promising for humans as well.

“Maybe in the future, when we are trying to develop an antidepressant that works in low-testosterone males, we can target some of the mechanisms by which testosterone acts, since it has numerous side effects,” he said.

Testosterone acts on many receptors and pathways in the brain, so the challenge is to develop a drug that delivers only the effect you want.

“A number of treatments are available for depression, but the drugs are not effective in all patients and the side effects can be serious, especially on the heart,” said biomedical sciences Professor Pradeep Bhide, director of the College of Medicine’s Center for Brain Repair.

“Therefore, there is an urgent need for safer and more efficacious drugs to treat depression.

The findings shed new light on the causes of depression and the role that hormones play in the disorder. Such insights are critical for the development of new drugs and diagnostic tests.

The study is published in the journal Biological Psychiatry.

Source: Florida State University