Effect of estradiol and dihydrotestosterone on hypergravity-induced MAPK signaling and occludin expression in human umbilical vein endothelial cells

Female astronauts have been reported to have a higher incidence of post-flight orthostatic intolerance (POI) compared with that of their male counterparts. POI may result from increased permeability of the endothelial cell (EC) layer in the vasculature. The goal of this study has been to determine whether estradiol (E-2) and dihydrotesterone (DHT) alter human umbilical vein ECs (HUVECs) responses to short term (10 min) hypergravity (1-3 g) mimicking the g force experienced by astronauts during liftoff. E-2 and DHT rapidly (within 5 min) activated MAPK (mitogen-activated protein kinase) in HUVEC at 1 g in a receptor-dependent manner. Liftoff inhibited MAPK phosphorylation, and rapid E-2 and DHT activation of MAPK was blocked. Liftoff simulation or brief (5-90 min) treatment with E-2 or DHT at 1 g had no effect on the expression of the EC tight-junction protein occludin. However, 24-h pre-treatment of HUVECs with E-2 and DHT prior to liftoff simulation significantly increased occludin expression, and hypergravity exposure did not alter this increase. These data provide evidence for a possible protective effect of E-2 and DHT on EC function as indicated by increased occludin; this may help maintain the integrity of EC tight junction and could thus retard or reduce the incidence of POI.