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. 2020 Oct;61(10):1308–1319. doi: 10.1194/jlr.RA119000479

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Copyright © 2020 Parks et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.

Author’s Choice—Final version open access under the terms of the Creative Commons CC-BY license.

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Fig. 2. — Biosynthetic pathways leading to neurosteroid synthesis. A: Illustration of steroidogenic enzymes produced in the mitochondria and endoplasmic reticulum leading to the synthesis of AlloP, testosterone, and CORT. B: Table outlining the steroidogenic enzymes associated with the respective numbers in A. Cholesterol is the precursor for all neurosteroid synthesis. Cholesterol is first metabolized by P450Scc (1) housed in the mitochondria to form pregnenolone. After exiting the mitochondria, pregnenolone can then be metabolized by 3β-hydroxysteroid dehydrogenase (2), located in the endoplasmic reticulum, to form PRG. PRG can then be metabolized by several different enzymes to form unique steroid metabolites. AlloP is formed via 5α-reductase (3) and 3α-hydroxysteroid dehydrogenase (4), respectively. Testosterone can be formed via P450c17 (3b) and 17β-hydroxysteroid dehydrogenase (4b), respectively. CORT can also be formed from 21-hydroxylase (3c) and 11β-hydroxylase (4c), respectively.