Neurosteroid Biosynthesis and Action in the Purkinje Cell

Abstract

It is now clearly established that steroids can be synthesized de novo by the vertebrate brain. Such steroids are called neurosteroids. To understand neurosteroid action in the brain, data on the regio- and temporal-specific synthesis of neurosteroids are needed. In the middle 1990s, the Purkinje cell, an important cerebellar neuron, was identified as a major site for neurosteroid formation in vertebrates. This discovery has allowed deeper insights into neuronal neurosteroidogenesis and biological actions of neurosteroids have become clear by the studies using the Purkinje cell as an excellent cellular model, which is known to play an important role in memory and learning processes. From the past 10 years of research on mammals, we now know that the Purkinje cell actively synthesizes progesterone and estradiol de novo from cholesterol during neonatal life, when cerebellar neuronal circuit formation occurs. Both progesterone and estradiol promote dendritic growth, spinogenesis, and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such neurosteroid actions that may be mediated by neurotrophic factors 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. The aim of this review is to summarize the current knowledge regarding the biosynthesis and biological actions of neurosteroids in the Purkinje cell during development.