Biosynthesis of Neurosteroids and Expression Profiles of Genes Responsible for Formation of 7α-OH-Preg and 7α-OH-DHEA in Mouse Brain Regions
(A) Biosynthetic pathways of 7α-hydroxylated neurosteroids. StAR transfers cholesterol to the mitochondria, where CYP11A1 catalyzes the conversion of cholesterol into pregnenolone. Pregnenolone is subsequently converted into various neurosteroids by hydroxylation and/or oxidation. Among the pathways, CYP7B1 catalyzes the 7α-hydroxylation of pregnenolone for the formation of 7α-OH-Preg. Alternatively, CYP17A1 catalyzes a two-step 17-oxydation pathway of pregnenolone for the formation of dehydroepiandrosterone (DHEA), which is then 7α-hydroxylated by CYP7B1 to form 7α-OH-DHEA.
(B–E) The expression levels of mRNAs for (B) StAR, (C) Cyp11a1, (D) Cyp17a1, and (E) Cyp7b1 were quantitated by RT-qPCR analysis of RNA samples prepared from various brain regions. CA1, hippocampal CA1 region; DG, dentate gyrus; Cg, cingulate cortex; MO, medial orbital cortex; PFC, prefrontal cortex. Data are normalized by mRNA levels of Rps29. The expression levels were presented as values relative to the maximal level in each panel. Values are shown as the mean ± SEM (n = 3–4).