{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T17:18:06Z","timestamp":1789406286262,"version":"build-2803163510"},"reference-count":65,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:p> Clear cells express the vacuolar proton-pumping H<jats:sup>+<\/jats:sup>-ATPase (V-ATPase) and acidify the lumen of the epididymis, a process that is essential for male fertility. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance in the epididymis, and a previous study showed binding of aldosterone exclusively to epididymal clear cells (Hinton BT, Keefer DA. Steroid Biochem 23: 231\u2013233, 1985). We examined here the role of aldosterone in the regulation of V-ATPase in the epididymis. RT-PCR showed expression of the mineralocorticoid receptor [MR; nuclear receptor subfamily 3, group C member 2 (NR3C2)] and 11-\u03b2-dehydrogenase isozyme 2 (HSD11\u03b22) mRNAs specifically in clear cells, isolated by fluorescence-activated cell sorting from B1-enhanced green fluorescent protein (EGFP) mice. Tail vein injection of adult rats with aldosterone, 1,2-dioctanoyl-sn-glycerol (DOG), or 8-(4-chlorophenylthio)-cAMP (cpt-cAMP) induced V-ATPase apical membrane accumulation and extension of V-ATPase-labeled microvilli in clear cells in the caput epididymis but not in the cauda. V-ATPase activity was measured in EGFP-expressing clear cells using the intracellular pH (pH<jats:sub>i<\/jats:sub>)-sensing dye seminaphthorhodafluor-5F-5-(and 6)-carboxylic acid, acetoxymethyl ester acetate (SNARF-5F). Aldosterone induced a rapid increase in the rate of Na<jats:sup>+<\/jats:sup>- and bicarbonate-independent pH<jats:sub>i<\/jats:sub> recovery following an NH<jats:sub>4<\/jats:sub>Cl-induced acid load in clear cells isolated from the caput but not the cauda. This effect was abolished by concanamycin A, spironolactone, and chelerythrine but not myristoylated-protein kinase inhibitor (mPKI) or mifepristone. Thus aldosterone increases V-ATPase-dependent proton secretion in clear cells in the caput epididymis via MR\/NR3C2 and PKC activation. This study, therefore, identifies aldosterone as an active member of the RAAS for the regulation of luminal acidification in the proximal epididymis. <\/jats:p>","DOI":"10.1152\/ajpcell.00410.2012","type":"journal-article","created":{"date-parts":[[2013,6,13]],"date-time":"2013-06-13T04:24:04Z","timestamp":1371097444000},"page":"C436-C446","source":"Crossref","is-referenced-by-count":22,"title":["Circulating aldosterone induces the apical accumulation of the proton pumping V-ATPase and increases proton secretion in clear cells in the caput epididymis"],"prefix":"10.1152","volume":"305","author":[{"given":"Jeremy W.","family":"Roy","sequence":"first","affiliation":[{"name":"Center for Systems Biology\/Program in Membrane Biology\/Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts; and"},{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hill","sequence":"additional","affiliation":[{"name":"Center for Systems Biology\/Program in Membrane Biology\/Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts; 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