# Named the unexpected hormone that protects men from stress and depression

The hormone estrogen, which is traditionally considered "female," has turned out to be a crucial protective factor for the male brain against stress and depression. This conclusion was reached by an international team of neurobiologists, whose work was published in the journal Molecular Psychiatry.

The study, led by Polymnnia Georgiou, showed that part of the testosterone in the male brain is converted with the help of the enzyme aromatase into the active form of estrogen - 17β-estradiol. It is this hormone, as confirmed by experiments, that prevents the development of "depression-like" behavior in male mice subjected to stress.

To understand the mechanism, the scientists created an experimental model including two factors - reduction in sex hormone levels and mild social stress. After removal of the testicles, which produce testosterone, male mice became more susceptible to stress: they avoided interaction with other individuals and lost interest in pleasant stimuli, such as the scent of females.

However, administration of 17β-estradiol completely eliminated these symptoms - the animals remained active and maintained their interest in pleasures. This confirmed that stress resistance is provided by estrogen, not testosterone.

A key element of this mechanism turned out to be the protein - estrogen receptor beta (ERβ). Males with this receptor disabled developed signs of depression, whereas the absence of receptor alpha did not cause such effects. Interestingly, females showed the opposite reaction: the absence of ERβ, on the contrary, increased their stress resistance. This indicates significant differences in hormonal regulation between men and women.

To exclude the influence of testosterone, the researchers applied the drug letrozole, which blocks its conversion to estrogen. After this, even healthy males became sensitive to stress and exhibited depressive behavior. Thus, the scientists definitively confirmed that it is estrogen that plays a protective role for the male brain.

Since direct application of estrogen in men can cause serious side effects, the scientists tested the compound DHED - an inactive form that is converted to estrogen only in the brain. The drug successfully prevented stress reactions without unwanted effects, opening new prospects for the development of safe antidepressants that act selectively on the male brain.