Pregnenolone serves as a precursor to other hormones, including dehydroepiandrosterone (DHEA) and progesterone. Pregnenolone is a steroid hormone involved in the steroidogenesis of progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. As such it is a prohormone. Pregnenolone is a GABA antagonist and increases neurogenesis in the hippocampus. Some people find pregnenolone improves energy, vision, memory, clarity of thinking, wellbeing, and often sexual enjoyment or libido. Pregnenolone may be considered a good brain enhancer in those who are deficient. Studies in rodents show pregnenolone to be one of the most effective and powerful memory boosters. Pregnenolone may increase levels of acetylcholine in the hippocampus and other memory regions in the brain. Some women report lessening of hot flashes or premenstrual symptoms. Pregnenolone and its sulfate ester are under investigation for their potential to improve cognitive and memory functioning.
Pregnenolone, like other steroids, consists of four interconnected cyclic hydrocarbons. It contains ketone and hydroxyl functional groups, two methyl branches, and a double bond at C5, in the B cyclic hydrocarbon ring. Like all steroid hormones, it is hydrophobic. Its esterified version, pregnenolone sulfate, is water-soluble. Pregnenolone can be converted to progesterone. The critical enzyme step is two-fold using a 3-beta-hydroxysteroid dehydrogenase and a delta 4-5 isomerase. The latter transfers the double bond from C5 to C4 on the A ring. Progesterone is the entry into the delta-4-pathway, resulting in production of 17-hydroxy progesterone and androstenedione, precursor to testosterone and estrone. Aldosterone and corticosteroids are also derived from progesterone or its derivatives.
Pregnenolone is synthesized from cholesterol. This conversion involves hydroxylation at the side-chain at C20 and C22 positions, with cleavage of the side-chain. The enzyme performing this task is cytochrome P450scc, located in the mitochondria, and controlled by pituitary tropic hormones, such as ACTH, FSH, LH. Pregnenolone can be converted to 17-hydroxy-pregnenolone by the enzyme 17α-hydroxylase (CYP17A1). Using this pathway, termed delta-5 pathway, the next step is conversion to dehydroepiandrosterone (DHEA) using a desmolase. DHEA is the precursor of androstenedione. Pregnenolone can be converted to androsta-5,16-dien-3 beta-ol by 16-ene synthetase. Pregnenolone and its sulfate, like dehydroepiandrosterone and its sulfate and progesterone, belong to the group of neurosteroids that are found in high concentrations in certain areas in the brain, and are synthesized there.