Neurosteroid dehydroepiandrosterone and brain function

Abstract

For last 30 years it became clear that DHEA and DHEAS are synthesized de novo in brain. Steroids synthesized in brain structures, were received the name "neurosteroids". In the review are submitted data on a biosynthesis and metabolism of DHEA(S) including its metabolism in fatty tissue where it serves as substrate for intracellular formation of its biologically active metabolites--estradiol and testosterone. The role of a sulfatase and sulfotransferase in mutual transformations of DHEA and DHEA-sulfate are analysed. Specific differences in DHEA synthesis in adrenals are surveyed. The adrenals of primates, both human beings and monkeys, produce free DHEA and DHEA-sulphate in large quantity. Their synthesis proceeds on Δ5-pathways: cholesterol-pregnenolone-17-hydroxypregnenolone-DHEA. Adrenals of other animas species, including rats and mice, don't synthesize DHEA. From the authors point of view, process of DHEAS penetration in brain structures include two mechanisms: transformation under steroid sulfatase action DHEAS in DHEA which freely gets through a blood-brain barrier and DHEAS passing through a hypothalamus which isn't protected by a blood-brain barrier. Results of researches on clinical application of DHEA as neurosteroid, with the analysis of its role in a course of Alzheimer's disease, distrurbances of cognitive function and other disorders of a CBS are presented also. The main neurobiological effects of DHEA(S) on brain structures which are studied on various models of animals include: neuroprotection, neurogenesis and neuronal survival, apoptosis, catecholamine synthesis and secretion. Neurosteroids have also antioxidant, anti-inflammatory and anti-glucocorticoid effects.