Molecular mechanisms of cytostatic and chemosensitizing action of gestagens

: In this study cytostatic and chemosensitizing actions of gestagens are described. Cytostatic mechanisms can be divided into estrogen-mediated and independent ones. The former include down-regulation of estrogen receptors, induction of 17?-hydroxysteroid dehydrogenase and estron sulfotransferase. The latter are MAP-kinase inhibition, induction of cell differentiation and apoptosis. Chemosensitization by gestagens is due to inhibition of P-glycoprotein, GST and MRP. Another putative chemosensitization mechanisms involves mitochondrial transition pore (MTP), at least for such gestagens as buterol and acetomepregenol. Elucidation of common mechanisms of MTP and MDR regulation and the possible role of MTP in chemosensitization is a new direction of investigations into the action of steroid hormones.