Neurosteroids in the Purkinje cell: biosynthesis, mode of action and functional significance

Neurosteroids are synthesized de novo from cholesterol in the brain. To understand neurosteroid action in the brain, data on the regio- and temporal-specific synthesis of neurosteroids are needed. Recently the Purkinje cell, an important cerebellar neuron, has been identified as a major site for neurosteroid formation in vertebrates. This is the first demonstration of de novo neuronal neurosteroidogenesis in the brain. Since this discovery, organizing actions of neurosteroids are becoming clear by the studies using the Purkinje cell as an excellent cellular model. In mammals, the Purkinje cell actively synthesizes progesterone and estradiol de novo from cholesterol during neonatal life. Both progesterone and estradiol promote dendritic growth, spinogenesis, and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such organizing actions that may be mediated by neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), contribute to the formation of cerebellar neuronal circuit during neonatal life. Allopregnanolone, a progesterone metabolite, is also synthesized in the cerebellum and acts on Purkinje cell survival in the neonate. This review summarizes the advances made in our understanding of the biosynthesis, mode of action and functional significance of neurosteroids in the Purkinje cell.