Progesterone

Progesterone has biphasic effects on proliferation of breast cancer cells; it stimulates growth in the first cell cycle, then arrests cells at G1/S of the second cycle accompanied by up-regulation of the cyclin-dependent kinase inhibitor, p21. Progesterone-mediated transcription is further prevented by overexpression of E1A, suggesting that CBP/p300 is required. ^[1] Progesterone drives a series of events where luminal cells probably provide Wnt4 and RANKL signals to basal cells which in turn respond by upregulating their cognate receptors, transcriptional targets and cell cycle markers. ^[2] Progesterone treatment increases the sensitivity of cortical synaptoneurosomes to GABA (i.e., decreased the EC50) and increases the maximal efficacy with which GABA stimulated Cl- transport (i.e., increased the Emax). ^[3]

Progesterone blocks the beneficial effect of estrogen on Abeta accumulation but not on behavioral performance in female 3xTg-AD mice. Progesterone significantly reduces tau hyperphosphorylation when administered both alone and in combination with estrogen. ^[4] Progesterone-treated rats are less impaired on a Morris water maze spatial navigation task than rats treated with the oil vehicle. Progesterone-treated rats also show less neuronal degeneration 21 days after injury in the medial dorsal thalamic nucleus, a structure that has reciprocal connections with the contused area. ^[5]