The generally accepted version of steroidogenesis is not free of uncertainties: Other tenable and possibly superior renditions may be invented

The neurosteroid pregnenolone is synthesized by a mitochondrial P450 enzyme other than CYP11A1 in human glial cells

“…Early experiments have shown that more pregnenolone and DHEA can be isolated from whole brain extracts when treated with FeSO 4 , FeCl 3 , lead tetraacetate, imidazole, or triethylamine (64). This idea was discussed by Lieberman et al, who suggested that the intermediates for pregnenolone synthesis found in vivo may be unstable oxygen radical products rather than stable intermediates that were isolated in in vitro experiments (65)(66)(67). The broad substrate specificity of CYP450 enzymes and the possibility that steroid synthesis can occur in multienzyme complexes pose uncertainties to the generally accepted pathway.…”

17-Hydroxyprogesterone in children, adolescents and adults

“…3 A biosynthetic pathway was defined and generally accepted, although deviations to the route are possible. 4 Prior to 1968, excess androgen production in CAH was defined by analysis of 17-ketosteroids (androgens) in urine, an obsolete colorimetric test since specific steroids can now be measured in blood. Pregnanetriol was known to be elevated in urine of patients with virilism before this was accepted as the main metabolite of 17-OHP.…”

Mitochondrial cytochrome P450 1B1 is involved in pregnenolone synthesis in human brain cells

“…The notion that there may be an alternative pathway for pregnenolone synthesis was proposed 2 decades ago ( 38 , 39 ), but there have been no studies to provide empirical evidence to show that such pathway or pathways exist or what factors might be involved. Our recent study was the first to show that pregnenolone production in human glial cells is in fact independent of CYP11A1 found in the classical pathway and that another mitochondrial CYP450 must be involved in pregnenolone synthesis instead ( 22 ).…”