title: Reverse effect of mammalian hypocalcemic cortisol in fish: cortisol stimulates Ca2+ uptake via glucocorticoid receptor-mediated vitamin D3 metabolism.
abstract: 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.
authors: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors: Chia-Hao
authors: CH
authors: Lin
authors: I-Lun
authors: IL
authors: Tsai
authors: Che-Hsien
authors: CH
authors: Su
authors: Deng-Yu
authors: DY
authors: Tseng
authors: Pung-Pung
authors: PP
authors: Hwang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D053493:Cholestanetriol 26-Monooxygenase; D005786:Gene Expression Regulation; D006854:Hydrocortisone / Q000502:physiology*; D018167:Receptors, Calcitriol / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000032:analysis / Q000235:genetics; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000032:analysis / Q000235:genetics
chemical_list: D018167:Receptors, Calcitriol; D011965:Receptors, Glucocorticoid; D050916:TRPV Cation Channels; D029961:Zebrafish Proteins; C505134:trpv6 protein, zebrafish; D053493:Cholestanetriol 26-Monooxygenase; D002118:Calcium; D006854:Hydrocortisone