{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:19:10Z","timestamp":1771305550108,"version":"3.50.1"},"reference-count":39,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:p> Medroxyprogesterone acetate (MPA), a widely used synthetic progestational contraceptive, occasionally leads to Cushingoid side effects such as hypertension, fluid retention, and centripetal obesity. We investigated the effect of MPA on classic mineralocorticoid target genes, \u03b1-epithelial Na channel (ENaC) and sgk1, in the collecting duct. In adrenalectomized mice, aldosterone, dexamethasone, and MPA increased \u03b1-ENaC mRNA levels in kidney cortex. MPA and dexamethasone, but not progesterone, dose dependently increased \u03b1-ENaC and sgk1 mRNA in M-1 and in Madin-Darby canine kidney-C7 cells, both collecting duct cell lines. The stimulatory effect of MPA and dexamethasone on \u03b1-ENaC expression was inhibited by RU-38486, a combined glucocorticoid receptor (GR) and progesterone receptor (PR) antagonist, but not by Org31710 , a pure PR antagonist. MPA and dexamethasone dose dependently increased \u03b1-ENaC promoter-driven luciferase activity in M-1 cells, which was not inhibited by Org31710 , indicating that MPA regulates \u03b1-ENaC in a PR-independent manner. When tested in HT29 cells, MPA could only stimulate \u03b1-ENaC-driven reporter activity when GR was coexpressed, confirming the requirement for functional GR in the transcriptional effect of MPA. The activation of steroid receptors such as GR can explain the apparent glucocorticoid effects of MPA, independent of PR activation. <\/jats:p>","DOI":"10.1152\/ajprenal.00062.2005","type":"journal-article","created":{"date-parts":[[2005,9,27]],"date-time":"2005-09-27T23:33:59Z","timestamp":1127864039000},"page":"F306-F312","source":"Crossref","is-referenced-by-count":30,"title":["Medroxyprogesterone acetate binds the glucocorticoid receptor to stimulate \u03b1-ENaC and sgk1 expression in renal collecting duct epithelia"],"prefix":"10.1152","volume":"290","author":[{"given":"Christie P.","family":"Thomas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang Z.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hemender S.","family":"Vats","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Bamberger CM, Else T, Bamberger AM, Ulrich Beil F, and Schulte HM. Dissociative glucocorticoid activity of medroxyprogesterone acetate in normal human lymphocytes. J Clin Endocrinol Metab 84: 4055\u20134061, 1999.","DOI":"10.1210\/jc.84.11.4055"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.24.3243"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Donckier JE, Michel LA, and Buysschaert M. Cushing syndrome and medroxyprogesterone acetate. Lancet 335: 1094, 1990.","DOI":"10.1016\/0140-6736(90)92663-3"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.48.1.231"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5476.119"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1007\/BF02967202"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1161\/hc4801.099737"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00085.2001"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00079.2002"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00143.2002"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910260209"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(96)00698-4"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2004.03.006"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-5994.1990.tb00433.x"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(69)90528-6"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.26.12480"},{"key":"R17","doi-asserted-by":"crossref","unstructured":"Lober J, Mouridsen HT, Salimtschik M, and Johansson E. Pharmacokinetics of medroxyprogesterone acetate administered by oral and intramuscular route. Acta Obstet Gynecol Scand Suppl 101: 71\u201374, 1981.","DOI":"10.3109\/00016348109157816"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1177\/000456329603300302"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030808"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00454.2003"},{"key":"R21","doi-asserted-by":"crossref","unstructured":"Merrin PK and Alexander WD. Cushing's syndrome induced by medroxyprogesterone. BMJ 301: 345, 1990.","DOI":"10.1136\/bmj.301.6747.345-a"},{"key":"R22","doi-asserted-by":"crossref","unstructured":"Mick VE, Itani OA, Loftus RW, Husted RF, Schmidt TJ, and Thomas CP. The \u03b1 subunit of the epithelial sodium channel is an aldosterone-induced transcript in mammalian collecting ducts, and this transcriptional response is mediated via distinct cis-elements in the 5\u2032 flanking region of the gene. Mol Endocrinol 15: 575\u2013588, 2001.","DOI":"10.1210\/me.15.4.575"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.20.12101"},{"key":"R24","unstructured":"Papaleo C, Carella C, Zito GA, Figlia A, Capuano F, and Amato G. ACTH and cortisol plasma levels in cancer patients treated with medroxyprogesterone acetate at high dosages. Chemioterapia 3: 220\u2013222, 1984."},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(87)90095-1"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.18.12431"},{"key":"R27","doi-asserted-by":"crossref","unstructured":"Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, and Thijssen JHH. Classification and pharmacology of progestins. Maturitas 46: 7\u201316, 2003.","DOI":"10.1016\/j.maturitas.2003.09.014"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1016\/0039-128X(95)00216-D"},{"key":"R29","unstructured":"Shotliff K and Nussey SS. Medroxyprogesterone acetate induced Cushing's syndrome. Br J Clin Pharmacol 44: 304, 1997."},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-111-9-758"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.23.2.0458"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00320.2001"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.48.30576"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-200409000-00010"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1159\/000070246"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.20.2673"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-7824(03)00136-7"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215696"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2003.08.005"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00062.2005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T19:04:17Z","timestamp":1567969457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00062.2005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,2]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2006,2]]}},"alternative-id":["10.1152\/ajprenal.00062.2005"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00062.2005","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,2]]}}}