Testosterone and Myelin Regeneration in the Central Nervous System

Abstract

Testosterone acts on the brain and spinal cord as an important regulator of neural functions, either by binding to the androgen receptor (AR) or via its aromatization to estradiol. Neurons have long been considered as its primary cellular target, but testosterone also plays a key role in the formation of myelin within the central nervous system (CNS). Remarkable features of CNS myelin are its plasticity and great capacity of regeneration. After a demyelinating lesion, new myelin sheaths are formed by oligodendrocytes recently generated from oligodendrocyte progenitor cells or by spared mature oligodendrocytes. Testosterone has allowed to demonstrate strong remyelinating effects, mediated by the AR receptor, in mouse models of toxin-induced demyelination. Enhancing these regenerative responses has become an objective for the treatment of demyelinating diseases, possibly including testosterone or AR ligands.