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Metabolism and Enzymology of Cholesterol and Steroids

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Handbook of Neurochemistry and Molecular Neurobiology

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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.

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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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Authors
  1. B. Stoffel-Wagner
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Department of Medical Chemistry, Biochemistry and Biotechnology, Via Saldini 50, 20133, Milan, Italy

    Guido Tettamanti

  3. Department of Internal Medicine Section of Biochemistry, University of Perugia, via del Giochetto, 06122, Perugia, Italy

    Gianfrancesco Goracci

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Stoffel-Wagner, B. (2009). Metabolism and Enzymology of Cholesterol and Steroids. In: Lajtha, A., Tettamanti, G., Goracci, G. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30378-9_4

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