Prégnénolone

Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineralocorticoids. In addition, pregnenolone is biologically active in its own right, acting as a neurosteroid. In addition to its role as a natural hormone, pregnenolone has been used as a medication and supplement; for information on pregnenolone as a medication or supplement, see the pregnenolone (medication) article. Pregnenolone and its 3β-sulfate, pregnenolone sulfate, like DHEA, DHEA sulfate, and progesterone, belong to the group of neurosteroids that are found in high concentrations in certain areas of the brain, and are synthesized there. Neurosteroids affect synaptic functioning, are neuroprotective, and enhance myelinization. Pregnenolone and its sulfate ester may improve cognitive and memory function. In addition, they may have protective effects against schizophrenia. Pregnenolone is an allosteric endocannabinoid, as it is a negative allosteric modulator of the CB1 receptor. Pregnenolone is involved in a natural negative feedback loop against CB1 receptor activation in animals. It prevents CB1 receptor agonists like tetrahydrocannabinol, the main active constituent in cannabis, from fully activating the CB1. A related compound AEF0117 has been derived from pregnenolone and is more specific for this type of activity. Pregnenolone has been found to bind with high, nanomolar affinity to microtubule-associated protein 2 (MAP2) in the brain. In contrast to pregnenolone, pregnenolone sulfate did not bind to microtubules. However, progesterone did and with similar affinity to pregnenolone, although unlike pregnenolone, it did not increase binding of MAP2 to tubulin. Pregnenolone was found to induce tubule polymerization in neuronal cultures and to increase neurite growth in PC12 cells treated with nerve growth factor.