Cholesterol is trafficked by StAR (sterodogenic acute regulatory protein) and TSPO (translocator protein 18 kDa) to the inner mitochondrial membrane where it is converted to pregnenolone by P450sc (cytochrome P450 side-chain cleavage). Pregnenolone is the precursor for progesterone that can undergo the two sequential A-ring reduction steps catalyzed by 5α-reductase and 3α-HSOR(3α-hydroxysteroid oxidoreductase) to form the neurosteroid allopregnanolone. Alternatively, in the zona reticulata of the adrenal cortex, P450c21 (cytochrome P450 21-hydroxylase) converts progesterone to DOC (deoxycorticosterone), which is the precursor for the neurosteroid THDOC (allotetrahydrodeoxycorticosterone). In the brain, this reaction appears to be mainly catalyzed by CYP2D isoenzymes, which can also conver allopregnanolone to THDOC.
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