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This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/C566    most recent 00418.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Sumanasekera, W. K. Articles by Klinge, C. M. Search for Related Content PubMed PubMed Citation Articles by Sumanasekera, W. K. Articles by Klinge, C. M.

VASCULAR BIOLOGY

Estradiol and dihydrotestosterone regulate endothelial cell barrier function after hypergravity-induced alterations in MAPK activity

¹Department of Biochemistry and Molecular Biology and Center for Genetics and Molecular Medicine, School of Medicine, ²Department of Physics, and ³Department of Bioengineering, Speed School of Engineering, University of Louisville, Louisville, Kentucky

Submitted 4 August 2006 ; accepted in final form 8 March 2007

Postflight orthostatic intolerance (POI) was reported to be higher in female than male astronauts and may result from sex-dependent differences in endothelial cell (EC) barrier permeability. Here the effect of 17-estradiol (E₂) and dihydrotestosterone (DHT) on the expression of the tight junction protein occludin, EC barrier function, and MAPK activation over time was tested after subjecting human umbilical vein EC (HUVEC) to brief hypergravity identical to that experienced by astronauts during liftoff (LO) into space. After LO hypergravity, HUVEC showed a time-dependent decrease in occludin correlating with an increase in paracellular permeability and a decrease in transendothelial electrical resistance, indicating a decrease in EC barrier function. LO hypergravity inhibited MAPK activation, which remained suppressed 4 h after LO. Inhibition of MAPK activation correlated with decreased phosphotyrosine occludin, decreased cytochrome-c oxidase activity, and increased paracellular permeability, suggesting a mechanism by which LO hypergravity decreased EC barrier function. Time-dependent differences in MAPK activation, decreased occludin, and EC barrier function between HUVEC treated with E₂ vs. DHT were observed. HUVEC showed delayed activation of MAPK with DHT, i.e., 4 h rather than 2 h for E₂, which correlated with decreased paracellular permeability and the observed sex differences in POI in astronauts. These data temporally separate E₂ and DHT effects in HUVEC and provide evidence for the possible protective roles of sex steroids on EC function after brief exposure to low hypergravity.

paracellular permeability; estrogen; androgen

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