The conversion of cholesterol to pregnenolone mediated by the enzyme cytochrome P450scc (Cyp11a1) is the first step of steroid hormone biosynthesis (Cyp11a1). Pregnenolone is biologically inactive. In the adrenal cortex and the gonads, it is turned into 17α-hydroxypregnenolone or progesterone.
In the brain, pregnenolone is converted into steroid hormones which have neuroprotective and activating effects: pregnenolone sulfate, an excitatory neurosteroid, as well as allopregnanolone and 7α-hydroxypregnenolone.
In some forms of congenital adrenal hyperplasia (17-hydroxylase insufficiency, 17,20-lyase insufficiency, P450-oxidoreductase insufficiency, the pregnenolone concentrations in plasma are increased. Congenital lipoid adrenal cortex hyperplasia is the most severe form of congenital adrenal hyperplasia, in which the synthesis of all steroid hormones, that is, glucocorticoids, mineralocorticoids and sex steroid hormones, is hindered due to a defect in the conversion of cholesterol to pregnenolone. The concentration of pregnenolone is low in the blood and high in the brain. It is reduced in elderly people or in patients with neurodegenerative diseases.
The determination of the pregnenolone level is useful for differential diagnostics in congenital adrenal hyperplasia (CAH).
The relationship between a deficiency of pregnenolone, which most of the steroid hormones are formed from, and a deficiency of androgens, estrogens and cortisol is controversially discussed.
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