Novel brain function: biosynthesis and actions of neurosteroids in neurons

Peripheral steroid hormones act on brain tissues through intracellular rece ptor-mediated mechanisms to regulate several important brain neuronal funct ions. Therefore, the brain is considered to be a target site of steroid hor mones. However, it is now established that the brain itself also synthesize s steroids de novo from cholesterol. The pioneering discovery of Baulicu an d his colleagues, using mammals, and our studies with non-mammals have open ed the door of a new research field. Such steroids synthesized in the brain are called neurosteroids. Because certain structures in vertebrate brains have the capacity to produce neurosteroids identification of neurosteroidog enic cells in the brain is essential to understand the physiological role o f neurosteroids in brain functions. Glial cells are generally accepted to b e the major site for neurosteroid formation. but the concept of neurosteroi dogenesis in brain neurons has up to now been uncertain. We recently demons trated neuronal neurosteroidogenesis in the blain and indicated that the Pu rkinje cell, a typical cerebellar neuron, actively synthesizes several neur osteroids de novo from cholesterol in both mammals and non-mammals. Pregnen olone sulfate, one of neurosteroids synthesized in the Purkinje neuron, may contribute to some important events in the cerebellum by modulating neurot ransmission. Progesterone, produced as a neurosteroid in this neuron only d uring neonatal life, may be involved in the promotion of neuronal and glial growth and neuronal synaptic contact ill the cerebellum. More recently, bi osynthesis and actions of neurosteroids in pyramidal neurons of the hippoca mpus were also demonstrated. These serve an excellent model for the study o f physiological roles of neurosteroids in the brain, because both cerebella r Purkinje neurons and hippocampal neurons play an important role in memory and learning. This paper summarizes the advances made in our understanding of neurosteroids, produced in neurons, and their actions. (C) 2000 Elsevie r Science ireland Ltd and the Japan Neuroscience Society. All rights reserv ed.