Glucocorticoids stimulate ENaC upregulation in bovine mammary epithelium.
Mammary epithelia produce an isotonic, low-Na(+) fluid that is rich in nutrients. Mechanisms that account for the low electrolyte concentration have not been elucidated, although amiloride-sensitive ion transport has been reported in some situations. We hypothesized that corticosteroid exposure modulates epithelial Na(+) channel (ENaC) expression and/or activity in bovine mammary epithelial cells. BME-UV cells were grown to confluent monolayers on permeable supports with a standard basolateral medium and apical medium of low-electrolyte, high-lactose composition that resembles the ionic composition of milk. Ion transport was assessed in modified Ussing flux chambers. Exposure to glucocorticoids (dexamethasone, cortisol, or prednisolone), but not aldosterone, increased short-circuit current (I(sc)), a sensitive measure of net ion transport, whereas apical exposure to amiloride or benzamil reduced corticosteroid-induced I(sc) close to basal levels. Quantitative RT-PCR indicated a glucocorticoid-induced increase in mRNA for beta- and gamma-ENaC, whereas alpha-ENaC mRNA expression was only mildly affected. Exposure to mifepristone (a glucocorticoid receptor antagonist), but not spironolactone (a mineralocorticoid receptor antagonist), precluded both the corticosteroid-induced elevation in amiloride-sensitive I(sc) and the induced changes in beta- and gamma-ENaC mRNA. We conclude that Na(+) movement across mammary epithelia is modulated by corticosteroids via a glucocorticoid receptor-mediated mechanism that regulates the expression of the beta- and gamma-subunits of ENaC. ENaC expression and activity could account for the low Na(+) concentration that is typical of milk.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-Y GENE-Y GENE-N CHEMICAL GENE-N GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
dexamethasone cortisol prednisolone aldosterone amiloride benzamil beta- and gamma-ENaC alpha-ENaC glucocorticoid receptor mineralocorticoid receptor mifepristone beta- and gamma-ENaC glucocorticoid receptor beta- and gamma-subunits of ENaC ENaC epithelial Na(+) channel ENaC ENaC spironolactone amiloride Na(+) Na(+) amiloride Na(+) Na(+) lactose