Neurosteroids in the cerebellar Purkinje neuron and their actions (Review)

Although the brain is a target site of steroid hormones supplied by peripheral steroidogenic glands, it is now established that the brain itself also synthesizes steroids dc novo from cholesterol in a variety of vertebrates. Such steroids synthesized in the brain are called neurosteroids. Because certain structures in vertebrate brains have the capacity to produce neurosteroids, the identification of neurosteroidogenic cells in the brain is essential to understand the physiological role of neurosteroids in brain functions. In the brain, glial cells are considered to play a major role in neurosteroid formation and metabolism. Both oligodendrocytes and astrocytes are the primary site for neurosteroidogenesis. However, the concept of neurosteroidogenesis in neurons in the brain has long been unclear. Recently, we demonstrated neurosteroidogenesis in the Purkinje cell, a typical cerebellar neuron, in mammals and other vertebrates. Pregnenolone sulfate, one of neurosteroids synthesized in the cerebellar Purkinje cell, may contribute to some important events in the cerebellum by modulating neurotransmission. Progesterone, produced as other neurosteroid in this neuron only during neonatal life, may be involved in the promotion of neuronal and glial growth and neuronal synaptic contact in the cerebellum. This review summarizes the advances made in our understanding of neurosteroids, produced in the Purkinje neuron, and their actions.