Cortisol was reported to downregulate body-fluid Ca 2+ levels in mammals but was proposed to show hypercalcemic effects in teleostean fish. Fish, unlike terrestrial vertebrates, obtain Ca 2+ from the environment mainly via the gills and skin rather than by dietary means, and have to regulate the Ca 2+ uptake functions to cope with fluctuating Ca 2+ levels in aquatic environments. Cortisol was previously found to regulate Ca 2+ uptake in fish; however, the molecular mechanism behind this is largely unclear. Zebrafish were used as a model to explore this issue. Acclimation to low-Ca 2+ fresh water stimulated Ca 2+ influx and expression of epithelial calcium channel (ecac), 11β-hydroxylase and the glucocorticoid receptor (gr). Exogenous cortisol increased Ca 2+ influx and the expressions of ecac and hydroxysteroid 11-beta dehydrogenase 2 (hsd11b2), but downregulated 11β-hydroxylase and the gr with no effects on other Ca 2+ transporters or the mineralocorticoid receptor (mr). Morpholino knockdown of the GR, but not the MR, was found to impair zebrafish Ca 2+ uptake function by inhibiting the ecac expression. To further explore the regulatory mechanism of cortisol in Ca 2+ uptake, the involvement of vitamin D 3 was analyzed. Cortisol stimulated expressions of vitamin D-25hydroxylase (cyp27a1), cyp27a1 like (cyp27a1l), 1α-OHase (cyp27b1) at 3 dpf through GR, the first time to demonstrate the relationship between cortisol and vitamin D 3 in fish. In conclusion, cortisol stimulates ecac expression to enhance Ca 2+ uptake functions, and this control pathway is suggested to be mediated by the GR. Lastly, cortisol also could mediate vitamin D 3 signaling to stimulate Ca 2+ uptake in zebrafish. © 2011 Lin et al.
CITATION STYLE
Lin, C. H., Tsai, I. L., Su, C. H., Tseng, D. Y., & Hwang, P. P. (2011). Reverse effect of mammalian hypocalcemic cortisol in fish: Cortisol stimulates Ca 2+ uptake via glucocorticoid receptor-mediated vitamin D 3 metabolism. PLoS ONE, 6(8). https://doi.org/10.1371/journal.pone.0023689
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