Pregnenolone

Pregnenolone induces a large, dose-related increase of both the rate and extent of MAP2-induced tubulin assembly, whereas progesterone, inactive per se, counteracted the stimulatory effect of Pregnenolone. Pregnenolone-increased assembly of microtubules produces a completely normal structure. ^[1] Pregnenolone preserves microtubule abundance and promotes cell movement during epiboly. ^[2] Pregnenolone results in dramatic reduction in GR nuclear localization in mouse hippocampal cell line (HT-22). Pregnenolone has neuroprotective effects against both glutamate and amyloid beta protein neuropathology. ^[3]

Pregnenolone sustains its proliferative activity in vivo and stimulates the growth of LNCaP-tumor xenografts in intact male SCID mice as well as in castrated animals. Pregnenolone is shown to activate transcription through the LNCaP androgen receptor (AR), but not the wild-type AR. ^[4] Pregnenolone results in a significant decrease in the accumulation of astrocytes in the proximity of the wound and in a decreased bromodeoxyuridine incorporation in reactive astrocytes of rats. ^[5] Pregnenolone administration results in elevations in downstream neurosteroids such as allopregnanolone, a molecule with neuroprotective effects that also increases neurogenesis, decreases apoptosis and inflammation, modulates the hypothalamic-pituitary-adrenal axis, and markedly increases GABA(A) receptor responses. Pregnenolone administration elevates pregnenolone sulfate, a neurosteroid that positively modulates NMDA receptors. ^[6]