Progesterone Promotes the Survival of Newborn Neurons in the Dentate Gyrus of Adult Male Mice

This study explored the impact of progesterone (P4) on neuron production and survival in the hippocampal dentate gyrus of adult male mice. Administering P4 at 4 mg/kg for 3 days significantly increased the number of 28- and 56-day-old BrdU+ cells, indicating enhanced neuron survival, but did not affect the number of 24/48-hour-old BrdU+ cells. The effect was specific to P4, as other hormones like androstenedione, testosterone, or estradiol did not replicate it, and it was not influenced by P4 metabolites. The P4 receptor (P4R) antagonist RU486 partially suppressed the effect, while inhibitors of Src, MEK, or PI3K completely suppressed it, suggesting that P4 acts through P4R and the Src-ERK and PI3K pathways. Additionally, P4 treatment improved spatial learning and memory, correlating with increased neuron survival. These findings indicated that P4 promoted neuron survival and cognitive function enhancement through specific pathways independent of cell proliferation.