Steroid-brain interactions are involved in a wide range of neurofunctional processes, and the consideration of regulatory loops has led to a better understanding of the action of hormone steroids on adaptive processes. The study of these interactions has become one of the most innovative chapters in modern neuroendocrinology. Classically, these interactions have been attributed to steroids synthesized in the periphery and acting in the brain. However, there is now evidence that some steroids can be neosynthesized in the brain (in neurons and glial cells) independently of peripheral sources. This discovery led to the concept of “neurosteroids”. Thus, the nervous system is the target of two types of steroids, distinguished by the site of production: steroids synthesized by peripheral tissues and neurosteroids synthesized directly by nerve cells. In parallel with this discovery, the term “neuroactive steroids” was proposed to describe the relatively rapid neuromodulatory action of steroids on membrane targets. Since the concept of neurosteroids was postulated, numerous studies have sought to understand the functional role of neurosteroids by investigating their synthetic pathways, targets of action, and neuromodulatory effects. In addition, considerable effort has been devoted in recent years to the development and validation of neurosteroid assays in the nervous system, with particular emphasis on measuring changes in endogenous neurosteroids under physiological and pathological conditions. Thus, metabolomic approaches, including lipidomics and steroidomics, are increasingly being studied to identify possible imbalances in lipid and steroid metabolism in relation to specific pathologies.

These approaches revealed a new role for neurosteroids, and in particular for pregnenolone, long thought to be an inactive precursor of neurosteroids.