Kwong, R.W., and Perry, S.F. (2013) Cortisol regulates epithelial permeability and sodium losses in zebrafish exposed to acidic water. The Journal of endocrinology. 217:253-264.
The effects of cortisol on epithelial permeability and sodium (Na+) handling during acid exposure were investigated in larval
zebrafish (Danio rerio). The results demonstrated that the whole-body absorption of the paracellular permeability marker polyethylene
glycol-4000 (PEG-4000) decreased with increasing levels of exogenous cortisol. Western blot analysis revealed that the abundance
of the epithelial tight junction proteins occludin-a and claudin-b was increased after cortisol treatment. Furthermore, translational
gene knockdown of claudin-b using an antisense morpholino oligonucleotide caused an increase in the permeability to PEG-4000,
which was mitigated by cortisol treatment, further suggesting a role for cortisol in reducing paracellular permeability. Exposure
to acidic water (pH 4.0 versus pH 7.6) caused an expected increase in the diffusive loss of Na+ and a decrease in whole-body
Na+ levels. These disruptive effects of acute acid exposure on Na+ balance were reduced by treatment of larvae with exogenous
cortisol. Translational knockdown of the glucocorticoid receptor (GR) abolished the effects of cortisol on epithelial PEG
permeability, suggesting that activation of GR was probably the major signalling pathway for reducing epithelial permeability.
During acid exposure, the epithelial PEG permeability in the GR morphants was significantly higher than in the control fish.
Additionally, GR morphants exhibited a more pronounced diffusive loss of Na+ than the control fish during acid exposure. These
findings suggest that cortisol may help to minimize the negative consequences of acid exposure on Na+ homeostasis via GR-mediated
reductions in epithelial permeability and paracellular Na+ loss.