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Estetrol and Its Effects on the Damaged Brain

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Sex Steroids' Effects on Brain, Heart and Vessels

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Abstract

Estrogens play an important role not only in the reproductive system but in the central nervous system as well. Major events of ontogenesis that 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 the 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 nervous 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 decreases 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 does not have any priority over the single 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 opening new directions for the use of E4 in clinical practice in neurological diseases.

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Authors and Affiliations

  1. Laboratory of Tumor Biology and Development, GIGA-Cancer, University of Liege, Liege, Belgium

    Ekaterine Tskitishvili & Jean Michel Foidart

  2. Department of Obstetrics and Gynecology, Faculty of Medicine, University of Liege, Liege, Belgium

    Jean Michel Foidart

  3. Department of Clinical Sciences, Faculty of Medicine, University of Liege, Liege, Belgium

    Jean Michel Foidart

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  1. Ekaterine Tskitishvili
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Editors and Affiliations

  1. Center for Innovation in Brain Sciencies-Department of Pharmacology and Neurology, College of Medicine, University of Arizona, Tucson, AZ, USA

    Roberta Diaz Brinton

  2. International School for Gynecological and Reproductive Endocrinology, International Society of Gynecological Endocrinology, Locarno, Switzerland

    Andrea R. Genazzani

  3. Department of Clinical and Experimental Medicine, Division of Obstetrics and Gynecology, University of Pisa, Pisa, Italy

    Tommaso Simoncini

  4. National Heart and Lung Institute, Imperial College London, London, UK

    John C. Stevenson

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Tskitishvili, E., Foidart, J.M. (2019). Estetrol and Its Effects on the Damaged Brain. In: Brinton, R., Genazzani, A., Simoncini, T., Stevenson, J. (eds) Sex Steroids' Effects on Brain, Heart and Vessels. ISGE Series. Springer, Cham. https://doi.org/10.1007/978-3-030-11355-1_4

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