From the Research
Pregnenolone acts primarily as a neurosteroid and precursor hormone in the body's steroid hormone synthesis pathway, serving as the starting material for the production of all steroid hormones, including progesterone, cortisol, aldosterone, estrogen, and testosterone, and its mechanism of action involves promoting ubiquitination and degradation of key proteins in the innate immune signaling to suppress inflammation, as well as modulating neurotransmitter receptors, particularly GABA and NMDA receptors 1. The mechanism of action of pregnenolone is complex and involves multiple pathways.
- It promotes ubiquitination and degradation of the TLR2/4 adaptor protein TIRAP and TLR2 in macrophages and microglial cells, suppressing the secretion of tumor necrosis factor α and interleukin-6 mediated through TLR2 and TLR4 signaling 1.
- Pregnenolone also functions as a neurosteroid that modulates neurotransmitter receptors, particularly GABA and NMDA receptors, enhancing GABA receptor function and producing calming effects, while also modulating glutamate activity at NMDA receptors, potentially improving cognitive function 2.
- Additionally, pregnenolone may influence neuronal myelination and have neuroprotective properties, and its levels have been observed to be decreased in neuroinflammatory diseases, emphasizing its role in neuroprotection and neuroregeneration 3.
- The body naturally produces pregnenolone from cholesterol in the mitochondria of various tissues, with the adrenal glands, gonads, and brain being primary production sites, and its synthesis is mediated by the mitochondrial monooxygenase system, involving adrenodoxin reductase, adrenodoxin, and a cytochrome P450 4.
- Pregnenolone's effects on mood, memory, and cognitive function are also influenced by its conversion to pregnenolone sulfate, which has excitatory effects by inhibiting GABA receptors and enhancing NMDA receptor activity, contributing to its dual modulation of inhibitory and excitatory neurotransmission 2.