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

Wasana K Sumanasekera¹, Gamini U Sumanasekera, Kathleen A Mattingly

¹Dept of Biochemistry and Molecular Biology and Center for Genetics and Molecular Medicine, School of Medicine, University of Louisville, KY 40292, USA.

American Journal of Physiology. Cell Physiology

|March 16, 2007

Summary

Sex hormones like estradiol and testosterone influence astronaut health. This study shows how these hormones affect endothelial cell barrier function during spaceflight, potentially explaining sex differences in postflight orthostatic intolerance.

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Area of Science:

Space medicine
Endocrinology
Cell biology

Background:

Postflight orthostatic intolerance (POI) is more prevalent in female astronauts.
Sex-dependent differences in endothelial cell (EC) barrier permeability may underlie POI.
Astronauts experience hypergravity during liftoff (LO).

Purpose of the Study:

To investigate the effects of 17beta-estradiol (E(2)) and dihydrotestosterone (DHT) on EC barrier function and MAPK activation under simulated LO hypergravity.
To explore the role of sex steroids in mitigating hypergravity-induced EC dysfunction.
To elucidate the mechanisms behind sex-based differences in POI.

Main Methods:

Human umbilical vein EC (HUVEC) were subjected to brief hypergravity simulating LO.
Changes in occludin expression, EC barrier permeability, transendothelial electrical resistance, and MAPK activation were measured over time.
HUVEC were treated with E(2) or DHT to assess their effects.

Main Results:

LO hypergravity decreased occludin expression, increased paracellular permeability, and reduced EC barrier function.
Hypergravity inhibited MAPK activation, which correlated with decreased occludin and increased permeability.
DHT delayed MAPK activation in HUVEC compared to E(2), correlating with reduced paracellular permeability.

Conclusions:

Hypergravity impairs EC barrier function via MAPK inhibition and decreased occludin.
Sex steroids (E(2) and DHT) differentially affect EC barrier function and MAPK activation.
These findings suggest a protective role for sex steroids in maintaining EC integrity during spaceflight, potentially explaining sex differences in POI.