PUBLICATION

Reverse Effect of Mammalian Hypocalcemic Cortisol in Fish: Cortisol Stimulates Ca Uptake via Glucocorticoid Receptor-Mediated Vitamin D(3) Metabolism

Authors
Lin, C.H., Tsai, I.L., Su, C.H., Tseng, D.Y., and Hwang, P.P.
ID
ZDB-PUB-110907-25
Date
2011
Source
PLoS One   6(8): e23689 (Journal)
Registered Authors
Hwang, Pung Pung, Tseng, Deng-Yu
Keywords
Hydrocortisone, Zebrafish, Embryos, Vitamins, Freshwater fish, Gene expression, Mammals, Fresh water
MeSH Terms
  • Animals
  • Calcium/metabolism*
  • Cholestanetriol 26-Monooxygenase
  • Gene Expression Regulation
  • Hydrocortisone/physiology*
  • Receptors, Calcitriol/metabolism*
  • Receptors, Glucocorticoid/metabolism*
  • TRPV Cation Channels/analysis
  • TRPV Cation Channels/genetics
  • Zebrafish
  • Zebrafish Proteins/analysis
  • Zebrafish Proteins/genetics
PubMed
21887296 Full text @ PLoS One
Abstract

Cortisol was reported to downregulate body-fluid Ca2+ levels in mammals but was proposed to show hypercalcemic effects in teleostean fish. Fish, unlike terrestrial vertebrates, obtain Ca2+ from the environment mainly via the gills and skin rather than by dietary means, and have to regulate the Ca2+ uptake functions to cope with fluctuating Ca2+ levels in aquatic environments. Cortisol was previously found to regulate Ca2+ 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-Ca2+ fresh water stimulated Ca2+ influx and expression of epithelial calcium channel (ecac), 11β-hydroxylase and the glucocorticoid receptor (gr). Exogenous cortisol increased Ca2+ 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 Ca2+ transporters or the mineralocorticoid receptor (mr). Morpholino knockdown of the GR, but not the MR, was found to impair zebrafish Ca2+ uptake function by inhibiting the ecac expression. To further explore the regulatory mechanism of cortisol in Ca2+ uptake, the involvement of vitamin D3 was analyzed. Cortisol stimulated expressions of vitamin D-25hydroxylase (cyp27a1), cyp27a1 like (cyp27a1l), 1±-OHase (cyp27b1) at 3 dpf through GR, the first time to demonstrate the relationship between cortisol and vitamin D3 in fish. In conclusion, cortisol stimulates ecac expression to enhance Ca2+ uptake functions, and this control pathway is suggested to be mediated by the GR. Lastly, cortisol also could mediate vitamin D3 signaling to stimulate Ca2+ uptake in zebrafish.

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