Biosynthesis and biological actions of neurosteroids in the avian brain

Peripheral steroid hormones cross the blood-brain barriers, due to their chemically lipid solubility, and act on brain tissues through intracellular receptor-mediated mechanisms that regulate several important brain neuronal functions. Therefore, the brain is considered to be a target site of peripheral steroids. In contrast to this classic concept, new findings have shown that the brain itself also synthesizes steroids de novo from cholesterol through mechanisms at least partly independent of peripheral steroido-genic glands. The pioneering discovery of Baulieu and his colleagues, using rodents, has opened the door to a new research field. In contrast to mammalian studies, little has been known regarding de novo steroidogenesis in the brain of nonmammalian vertebrates. We have therefore looked for steroids formed from cholesterol in the brain of birds. A series of our studies over the past decade has demonstrated that the avian brain itself can synthesize steroids de novo. Independently, Schlinger's laboratory has also contributed to this exciting area of research. Thus, the formation of several steroids from cholesterol in the brain is now known to occur in birds as well as other vertebrates. Such steroids synthesized de novo in vertebrate brains are called neurosteroids. Neurosteroids may act on neuronal tissues through genomic and nongenomic actions to regulate several important neuronal functions. This paper summarizes the advances made in our understanding of biosynthesis of neurosteroids in the avian brain. This paper also describes what is currently known about biological actions of neurosteroids.