Scientists at the University Medical Center Mannheim have found that the female hormone estrogen protects kidney cells from ferroptosis, an iron-dependent, regulated form of cell death. The results of the study were published in the journal Nature.
Doctors have long known that women are less prone to acute kidney failure than men; this fact has been confirmed by epidemiological data since the 1940s. However, the mechanism of this protective effect remained unclear for a long time.
Experiments on female and male mice have shown that the main female sex hormone blocks ferroptosis. This explains why the protective effect weakens during menopause, when its production decreases. The main role is played by estrogen itself and its hydroxylated derivatives, in particular, 2-hydroxyestradiol; they induce a complex protective cascade involving genomic and non-genomic mechanisms.
Scientists have explained that estrogen works in two ways. It not only acts as a natural "barrier" against ferroptosis, but also binds to a special receptor in the cells, "turning on" the body's defense reactions. These reactions reduce the level of harmful molecules that damage the tissue and keep important elements of the cell membrane intact.
The authors believe that the results help explain the differences in the risk of kidney disease in men and women and open the way for new therapeutic approaches.
"Our results may also have implications for cardiology. They suggest that ferroptosis plays an important role in sex differences in diseases such as heart attack and stroke, from which women are generally better protected than men," said Professor Andreas Linkermann, director of the center's 5th Medical Clinic and co-author of the study.
