Figure 1.

Neurosteroid and sex steroid biosynthetic pathway in the human brain. (A) The main steps of neuroactive steroid synthesis are shown. The initial and limiting step involves P450scc activity catalyzing the metabolism of cholesterol to pregnenolone (PREG), the precursor of all neurosteroids and sex steroids. Then, PREG is transformed to progesterone (PROG) and its 5α-reduced and 5α,3α-reduced metabolites (5α-DHP and allopregnanolone). These steps involve 3β-HSD and the 5α-reductase/3α-HSD complex enzymes. PREG and PROG are precursors of DHEA and androstenedione, respectively. PREGS and DHEAS are produced from PREG and DHEA by sulfotransferases and can in turn be desulfated by sulfatases. The so-called sex steroids are testosterone produced from androstenedione by 17β-HSD activity and E2 from testosterone aromatization. (B) Location of steroidogenic enzyme in the human brain regions. Enzyme mRNA, protein and activity are present, except for P450scc whose mRNA was only expressed. P450scc: P450side chain cleavage, 3β-HSD: 3β-hydroxysteroid dehydrogenase-Δ5 (Δ4 isomerase, 3α-HSD: hydrosteroid dehydrogenase, 3β-HST: 3β-hydroxysteroid sulfotransferase, 17β-HSD: 17β-hydroxysteroid dehydrogenase 5α-DHP: 5α-dihydroprogesterone; 3α,5α-THP: 3α,5α-tetrahydroprogesterone.