title: Glucocorticoids stimulate ENaC upregulation in bovine mammary epithelium.
abstract: 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.
authors.affiliation: Department of Anatomy and Physiology, 228 Coles Hall, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Quesnell
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Han
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Schultz
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003907:Dexamethasone / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism* / Q000494:pharmacology; D006854:Hydrocortisone / Q000378:metabolism; D007774:Lactation / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials; D015735:Mifepristone / Q000494:pharmacology; D008892:Milk / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011239:Prednisolone / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D053503:Epithelial Sodium Channels; D005938:Glucocorticoids; D021122:Protein Subunits; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D026941:Sodium Channel Blockers; D015735:Mifepristone; D000584:Amiloride; D003907:Dexamethasone; D012964:Sodium; D011239:Prednisolone; D006854:Hydrocortisone