title: Effect of estradiol and dihydrotestosterone on hypergravity-induced MAPK signaling and occludin expression in human umbilical vein endothelial cells.
abstract: 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.
authors.affiliation: Department of Biochemistry & Molecular Biology, Center for Genetics and Molecular Medicine, School of Medicine, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Wasana K
authors.initials: WK
authors.lastname: Sumanasekera
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Margarita
authors.initials: M
authors.lastname: Ivanova
authors.forename: Dwight D
authors.initials: DD
authors.lastname: Morgan
authors.forename: Edouard L
authors.initials: EL
authors.lastname: Noisin
authors.forename: Robert S
authors.initials: RS
authors.lastname: Keynton
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Klinge
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D013196:Dihydrotestosterone / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018471:Hypergravity / Q000009:adverse effects*; D007024:Hypotension, Orthostatic / Q000209:etiology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D062793:Occludin; D013026:Space Flight; D018561:Space Simulation / Q000009:adverse effects; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D013196:Dihydrotestosterone; D004958:Estradiol