Neuroactive steroids are a class of endogenous neuromo-dulators that influence brain processes in fundamental ways that affect mood, behavior and all organ systems controlled by brain function. Pioneering work from Baulieu and collaborators in the early 1980s demonstrated the persistence of substantial amounts of pregnenolone, progesterone, dehydroepiandrosterone (DHEA) and their sulfate metabolites in the brain of adrenalectomized/ gonadectomized animals. This suggests that the brain was capable of local synthesis of these steroids that were thus termed ► Neurosteroids. Subsequent studies have shown that neurons and glial cells in the brain have the ability to locally synthesize neurosteroids de novo from cholesterol (Baulieu 1998). The biosynthetic pathway for neuroactive steroids is shown in Fig. 1. Neuroactive steroids with inhibitory activity on neurons are shown in blue while steroids with excitatory activity on neurons are show in red.
The classical action of steroid hormones is to regulate transcriptional activity and protein biosynthesis over minutes to hours via interaction with nuclear steroid receptors. However, neuroactive steroids have the ability to rapidly (milliseconds to seconds) alter the neuronal excitability by binding to membrane receptors such as ion channels or receptors in the plasma membrane (see Paul
Neuroactive Steroids. Fig. 1. Biosynthetic pathway for neuroactive steroids. While neuroactive steroids with inhibitory activity on neurons are shown in blue, neuroactive steroids with excitatory activity on neurons are show in red. 3a,5a-THP (3a,5a)-3-hydroxypregnan-20-one; 3a,5b-THP (3a,5b)-3-hydroxypregnan-20-one; 3a,5a-THDOC (3a,5a)-3,21-dihydroxypregnan-20-one; 3a,5b-THDOC (3a,5b)-3,21-dihydroxypregnan-20-one; 3fi-HSD 3b-hydroxysteroid dehydrogenase; 5a/b-R 5a/5b-reductase; 3a-HSD 3a-hydroxysteroid dehydrogenase; 17fi-HSD 17b-hydroxysteroid dehydrogenase.
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