Neurosteroids: Biosynthesis and function of these novel neuromodulators

Over the past decade, it has become clear that the brain is a steroidogenic organ. The steroids synthesized by the brain and nervous system, given the name neurosteroids, have a wide variety of diverse functions. In general, they mediate their actions, not through classic steroid hormone nuclear rec eptors, but through ion-gated neurotransmitter receptors. This paper summar izes what is known about the biosynthesis of neurosteroids, the enzymes med iating these reactions, their localization during development and in the ad ult, and their function and mechanisms of action in the developing and adul t central and peripheral nervous systems. The expression of the steroidogen ic enzymes is developmentally regulated, with some enzymes being expressed only during development, while others are expressed during development and in the adult. These enzymes are expressed in both neurons and glia, suggest ing that these two cell types must work in concert to produce the appropria te active neurosteroid. The functions attributed to specific neurosteroids include modulation of GABA(A), and NMDA function, modulation of sigma recep tor function, regulation of myelinization, neuroprotection, and growth of a xons and dendrites. Neurosteroids have also been shown to modulate expressi on of particular subunits of GABA(A) and NMDA receptors, providing addition al sites at which these compounds can regulate neural function. The pharmac ological properties of specific neurosteroids are described, and potential uses of neurosteroids in specific neuropathologies and during normal aging in humans are also discussed. (C) 2000 Academic Press.