Novel cerebellar function: Neurosteroids in the purkinje neuron and their genomic and nongenomic actions

Peripheral steroid hormones cross the blood-brain barriers due to their chemically lipid solubility, and act on brain tissues through intracellular receptormediated mechanisms which regulate several important brain neuronal functions. ^1,2 Therefore, the brain is considered to be a target site of peripheral steroids. Additionally, new findings have been obtained which suggest that the nervous system itself may form steroids de novo. The pioneering discovery of Baulieu and his colleagues, using rodents, has opened the door of a new research field for many laboratories. Pregnenolone and dehydroepiandrosterone, as unconjugated steroids, and their fatty acid or sulfate esters, accumulate within the brains of several mammalian species. ^3-10 The brain content of these steroids remains constant even after the removal of peripheral steroids by procedures such as adrenalectomy, castration, and hypophysectomy. This suggests that the brain can synthesize steroids de novo. ^3-9 In contrast to extensive mammalian studies, little is known regarding de novo steroidogenesis in the brain of nonmammalian vertebrates. We therefore looked for steroids, formed from cholesterol, in the brains of both avian ^11-14 and amphibian species. ¹⁵ Independently, other groups such as the Vaudry laboratory ¹⁶ and the Schlinger laboratory ¹⁷ have also contributed to this area. The formation of several steroids from cholesterol is now known to occur in nonmammalian vertebrates. Such steroids synthesized in vertebrate brains are called neurosteroids.