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Metabolism and Enzymology of Cholesterol and Steroids

  • B. Stoffel-Wagner
Reference work entry

Abstract:

This chapter summarizes the current knowledge on the metabolism of steroids in the human brain, the enzymes mediating these reactions, their localization, and the putative effects of steroids in the brain. The presence of the steroidogenic enzymes cytochrome P450SCC, aromatase, 5α-reductase, 3α-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and steroid sulfatase in human brain has now been firmly established by molecular biological and biochemical studies. Their presence in the cerebral cortex and in the subcortical white matter indicates that various cell types, either neurons or glial cells, are involved in the biosynthesis of neuroactive steroids in the brain. The following functions are attributed to specific neuroactive steroids: modulation of GABAA, N-methyl-d-aspartate (NMDA), nicotinic, muscarinic, serotonin (5-HT3), kainate, glycine and sigma receptors, neuroprotection, and induction of neurite outgrowth, dendritic spines, and synaptogenesis. The first clinical investigation in humans produced evidence for an involvement of neuroactive steroids in conditions such as depressive disorders, catamenial epilepsy, fatigue during pregnancy, premenstrual syndrome, and postpartum depression. Further and improved knowledge of the biochemical pathways of steroidogenesis and the actions of neuroactive steroids on the brain may enable new perspectives in the understanding of the physiology of the human brain as well as in the pharmacological treatment of its disturbances.

Keywords

Subcortical White Matter Aromatase Activity Neuroactive Steroid CYP11A1 mRNA Steroidogenic Enzyme 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations:

3β-HSD

3β-hydroxysteroid dehydrogenase

DHEA

dehydroepiandrosterone

DHEAS

dehydroepiandrosterone sulfate

GABAA

γ-aminobutyric acid A

NMDA

N-methyl-d-aspartate

OATP-A

organic anion transporter polypeptide-A

OATP

organic anion transporter polypeptides

17β-HSD

17β-hydroxysteroid dehydrogenase

STS

steroid sulfatase

SULT2

hydroxysteroid sulfotransferase

3α-HSD

3α-hydroxysteroid dehydrogenase

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© Springer Science+Business Media, LLC 2009

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  • B. Stoffel-Wagner

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