Pregnenolon

Pregnenolone is a steroid hormone precursor and neurosteroid that is biosynthesized from cholesterol. It sits at the top of the steroidogenesis pathway and provides the starting material for the production of progesterone, androgens, estrogens, and other downstream steroids. In humans, pregnenolone is produced primarily in the adrenal glands and gonads, with additional synthesis in the brain where it also acts as a local neuromodulator.

The conversion of cholesterol to pregnenolone occurs in the mitochondria by the cholesterol side-chain cleavage enzyme, known as CYP11A1 or P450scc. This step is rate-limiting in steroid production. Pregnenolone can be further metabolized by enzymes such as 3β-hydroxysteroid dehydrogenase to progesterone, and then through other enzymatic steps to androgens and estrogens. In the brain, pregnenolone is produced by neurons and glial cells and can be transformed into neurosteroids such as allopregnanolone and pregnenolone sulfate, which modulate neuronal signaling.

Biological roles of pregnenolone extend beyond serving as a hormone precursor. It and its metabolites act as neuromodulators and have been studied for effects on learning, memory, mood, and neuroprotection. Research has explored potential therapeutic applications in neurodegenerative and psychiatric conditions, but clinical evidence remains inconclusive and no regulatory body approves pregnenolone as a medical treatment.

Safety and regulation vary by country. Pregnenolone is available as a dietary supplement in some jurisdictions, but long-term safety data are limited. Potential hormonal side effects, interactions with other hormone therapies, or hormonal imbalances may occur at higher doses, and use should be discussed with a healthcare professional.