Neurosteroids: metabolism and activities
The work to describe the synthesis and metabolic pathways of neurosteroids, and establish their physiological and pathological function and mechanism (s) of action has encountered some major difficulties:
Many analytical problems, qualitative and quantitative, were encountered because of the low concentration and the lipoidal nature of neurosteroids, which have to be separated from the highly lipidic constituents of neural tissues. Strictly controlled conditions had to be established, since neurosteroid concentrations vary according to the time of day, the lighting schedule, the food, the presence of other animals, the habituation to handling, and so on.
The overall dynamics of the synthesis of neurosteroids is unknown, since their turnover cannot be determined and no appropriate techniques are available for describing their compartmentation.
Quantitative aspects are particularly difficult to master since many neurosteroids are also secreted by peripheral glands, may cross the blood—brain barrier and also easily attain peripheral nerves, eventually mixing with neurosteroids. In fact, the respective distribution and contribution of steroids imported into the nervous system and of those synthetized in situ remain difficult to assess and consequently, we do not necessarily know what the respective targets are.
Binding studies and thus the search for receptors are especially hard in a lipid-rich milieu, as often encountered in work with nervous tissue and its membranes, again because of the liposolubility of steroids.