Estetrol and the brain

peer reviewedEstrogens play an important role not only in reproductive system but in the central nervous system as well. Major events of ontogenesis occur earlier in pregnancy are connected to the formation of estrogen receptors and expression of estrogens leading to the normal physiological development of the central nervous system, though development of brain by itself is a complex process and lasts during the whole pregnancy. Estetrol (E4) is a recently described natural estrogen with four hydroxyl-groups that is synthesized exclusively during pregnancy by the human fetal liver. Its role in the central nerovus system is not fully understood. Our studies showed for the first time and proved impressive antioxidative effects of E4 in vitro and proved its tremendous neuroprotective, promyelinating, neurogenic and cerebro-angiogenic properties in vivo. E4 dicreases brain damage markers (S100B and GFAP) in blood assuming that E4 attenuates neonatal hypoxic-ischemic encephalopathy in vivo. We have also shown that the combined use of E4 with other steroids do not have any priority over the signle use of E4. E4’s antioxidative actions mostly depend on ERα and ERβ, whereas neurogenesis and possibly promyelinating activities might be realized through ERβ. Taken together our studies suggest importance of E4 treatment possibly not only in neonates but in adults with different neurological diseases like that that opening new directions for the use of E4 in clinical practice in neurological diseases