Testosterone, the most important male sex hormone, has an antidepressant effect, confirms the latest American research. The authors of the work in the journal Biological Psychiatry explain why this is happening.
As recalled in the introduction to this article, previous human and animal studies have suggested that testosterone may protect against depression.
For example, it is known that compared to men, women are twice as likely to develop mood disorders. In turn, the gentlemen of the so-called hypogonadism – a defect that causes the testes to fail to produce or not produce enough testosterone – they are more likely to suffer from depression and anxiety disorders. Research also shows that testosterone replacement therapy relieves these disorders.
However, the mechanisms responsible for the beneficial effects of the male hormone on mood are not well understood. Meanwhile, a better understanding of them would allow scientists to develop new treatments for depression.
Researchers from Florida State University in Tallahassee (Florida, USA) conducted experiments on adult male rats whose testicles were excised. The animals developed behaviors consistent with the depressive symptoms in humans, which were resolved by the administration of testosterone.
Researchers focused on the effects of this hormone on processes in the hippocampus, a structure in the brain that plays a pivotal role in regulating memory, emotion and mood, and developing depression. They took into account not only the formation of new neurons in it (so-called neurogenesis), but also changes in the activity of genes that regulate the response of cells to stress factors.
It turned out that the antidepressant effect of testosterone was not related to its beneficial effects on the survival of neurons or stimulation of their growth in the hippocampus, which is observed with other classic drugs for depression, including fluoxetine (the famous Prozac) or imipramine (an older antidepressant from the group of the so-called tricyclic).
Instead, researchers showed that the hormone exerts its effect by regulating the activity of the ERK2 kinase gene in the dentate gyrus of the hippocampus.
When ERK2 activity in this area of the brain was reduced in testosterone-free rats, the animals showed symptoms of anhedonia, ie they were not able to feel pleasure, which is one of the hallmarks of depression.
In contrast, over-activation of ERK2 alleviated the condition.
According to the authors of the study, this suggests that the proper functioning of the ERK2 gene is crucial for the antidepressant effect of testosterone. Scientists hope that their discovery will help develop new treatments for depression in the future.
Read more: Does testosterone make men weaker?