{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T20:13:46Z","timestamp":1790540026183,"version":"4.1.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"French Ministry of Health","award":["CRC12122"],"award-info":[{"award-number":["CRC12122"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In rodents, the stimulation of adrenal progesterone is necessary for renal adaptation under potassium depletion. Here, we sought to determine the role of progesterone in adrenal adaptation in potassium-depleted healthy human volunteers and compared our findings with data collected in patients with Gitelman syndrome (GS), a salt-losing tubulopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twelve healthy young men were given a potassium-depleted diet for 7\u2009days at a tertiary referral medical centre (NCT02297048). We measured by liquid chromatography coupled to tandem mass spectroscopy plasma steroid concentrations at Days 0 and 7 before and 30\u2009min after treatment with tetracosactide. We compared these data with data collected in 10 GS patients submitted to tetracosactide test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The potassium-depleted diet decreased plasma potassium in healthy subjects by 0.3\u2009\u00b1\u20090.1\u2009mmol\/L, decreased plasma aldosterone concentration by 50% (P\u2009=\u20090.0332) and increased plasma 17-hydroxypregnenolone concentration by 45% (P\u2009=\u20090.0232) without affecting other steroids. CYP17 activity, as assessed by 17-hydroxypregnenolone\/pregnenolone ratio, increased by 60% (P\u2009=\u20090.0389). As compared with healthy subjects, GS patients had 3-fold higher plasma concentrations of aldosterone, 11-deoxycortisol (+30%) and delta 4-androstenedione (+14%). Their post-tetracosactide progesterone concentration was 2-fold higher than that of healthy subjects and better correlated to plasma potassium than to plasma renin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The increase in 17-hydroxypregnenolone concentration after mild potassium depletion in otherwise healthy human subjects suggests that 17 hydroxylation of pregnenolone prevents the increase in progesterone observed in potassium-depleted mice. The unexpected over-response of non-mineralocorticoid steroids to tetracosactide in GS subjects suggests that the adrenal system not only adapts to sodium depletion but may also respond to hypokalaemia.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ndt\/gfz135","type":"journal-article","created":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T19:10:59Z","timestamp":1560280259000},"page":"1901-1908","source":"Crossref","is-referenced-by-count":10,"title":["Adrenal adaptation in potassium-depleted men: role of progesterone?"],"prefix":"10.1093","volume":"35","author":[{"given":"Anne","family":"Blanchard","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Assistance Publique H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Centre d\u2019Investigation Clinique, Paris, France"},{"name":"INSERM, CIC-1418, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Brailly Tabard","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine Paris-Sud, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France"},{"name":"Assistance Publique H\u00f4pitaux de Paris, H\u00f4pital de Bic\u00eatre, Service de G\u00e9n\u00e9tique Mol\u00e9culaire, Pharmacog\u00e9n\u00e9tique et Hormonologie, Le Kremlin-Bic\u00eatre, France"},{"name":"Inserm 1185 Facult\u00e9 de M\u00e9decine Paris-Sud, Paris-Saclay, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonin","family":"Lamaziere","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Saint-Antoine, Plateforme de M\u00e9tabolomique, Peptidomique et de Dosage de M\u00e9dicaments, Paris, France"},{"name":"INSERM ERL1157, Le Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Bergerot","sequence":"additional","affiliation":[{"name":"INSERM, CIC-1418, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Zhygalina","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Assistance Publique H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Centre d\u2019Investigation Clinique, Paris, France"},{"name":"INSERM, CIC-1418, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Lorthioir","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Assistance Publique H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Centre d\u2019Investigation Clinique, Paris, France"},{"name":"INSERM, CIC-1418, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Jacques","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Unit\u00e9 de recherche clinique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Hourton","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Unit\u00e9 de recherche clinique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Azizi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, Paris, France"},{"name":"Assistance Publique H\u00f4pitaux de Paris, H\u00f4pital Europ\u00e9en Georges Pompidou, Centre d\u2019Investigation Clinique, Paris, France"},{"name":"INSERM, CIC-1418, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Crambert","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, Universit\u00e9 Paris Descartes, Sorbonne Paris Cit\u00e9, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006, Paris, France"},{"name":"CNRS ERL 8228\u2014Centre de Recherche des Cordeliers\u2014Laboratoire de Physiologie R\u00e9nale et tubulopathies, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,1]]},"reference":[{"key":"2020110509411682700_gfz135-B1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1056\/NEJMra1313341","article-title":"An integrated view of potassium homeostasis","volume":"373","author":"Gumz","year":"2015","journal-title":"N Engl J Med"},{"key":"2020110509411682700_gfz135-B2","first-page":"F817","article-title":"Renal potassium transport: mechanisms and regulation","volume":"274","author":"Giebisch","year":"1998","journal-title":"Am J Physiol"},{"key":"2020110509411682700_gfz135-B3","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s00424-008-0593-3","article-title":"Regulation of potassium (K) handling in the renal collecting duct","volume":"458","author":"Wang","year":"2009","journal-title":"Pflugers Arch"},{"key":"2020110509411682700_gfz135-B4","doi-asserted-by":"crossref","first-page":"F693","DOI":"10.1152\/ajprenal.00605.2013","article-title":"H-K-ATPase type 2: relevance for renal physiology and beyond","volume":"306","author":"Crambert","year":"2014","journal-title":"Am J Physiol Renal Physiol"},{"key":"2020110509411682700_gfz135-B5","doi-asserted-by":"crossref","first-page":"2859","DOI":"10.1096\/fj.11-199711","article-title":"Circadian expression of H, K-ATPase type 2 contributes to the stability of plasma K(+) levels","volume":"26","author":"Salhi","year":"2012","journal-title":"Faseb J"},{"key":"2020110509411682700_gfz135-B6","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1681\/ASN.2013111156","article-title":"Mechanisms of renal control of potassium homeostasis in complete aldosterone deficiency","volume":"26","author":"Todkar","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"2020110509411682700_gfz135-B7","doi-asserted-by":"crossref","first-page":"F14","DOI":"10.1152\/ajprenal.00705.2010","article-title":"Conservation of Na+ vs. K+ by the rat cortical collecting duct","volume":"301","author":"Frindt","year":"2011","journal-title":"Am J Physiol Renal Physiol"},{"key":"2020110509411682700_gfz135-B8","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1146\/annurev.physiol.66.032102.112025","article-title":"Regulation of renal K transport by dietary K intake","volume":"66","author":"Wang","year":"2004","journal-title":"Annu Rev Physiol"},{"key":"2020110509411682700_gfz135-B9","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/ki.2011.15","article-title":"Chronic potassium depletion increases adrenal progesterone production that is necessary for efficient renal retention of potassium","volume":"80","author":"Elabida","year":"2011","journal-title":"Kidney Int"},{"key":"2020110509411682700_gfz135-B10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1152\/physiolgenomics.00055.2004","article-title":"Plasticity of mouse renal collecting duct in response to potassium depletion","volume":"19","author":"Cheval","year":"2004","journal-title":"Physiol Genomics"},{"key":"2020110509411682700_gfz135-B11","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/ki.2011.131","article-title":"Progesterone: not just a sex hormone anymore?","volume":"80","author":"Wingo","year":"2011","journal-title":"Kidney Int"},{"key":"2020110509411682700_gfz135-B12","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1210\/endo-123-6-2675","article-title":"Quantification of P450scc, P450(17) alpha, and iron sulfur protein reductase in Leydig cells and adrenals of inbred strains of mice","volume":"123","author":"Perkins","year":"1988","journal-title":"Endocrinology"},{"key":"2020110509411682700_gfz135-B13","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1021\/bi9821059","article-title":"Biochemical differences between rat and human cytochrome P450c17 support the different steroidogenic needs of these two species","volume":"38","author":"Brock","year":"1999","journal-title":"Biochemistry"},{"key":"2020110509411682700_gfz135-B14","first-page":"186","article-title":"A liquid chromatography\/tandem mass spectometry profile of 16 serum steroids, including 21-deoxycortisol and 21-deoxycorticosterone, for management of congenital adrenal hyperplasia","volume":"1","author":"Fiet","year":"2017","journal-title":"J Endocr Soc"},{"key":"2020110509411682700_gfz135-B15","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/ki.1980.38","article-title":"Response of the collecting duct to disturbances of acid-base and potassium balance","volume":"17","author":"Hansen","year":"1980","journal-title":"Kidney Int"},{"key":"2020110509411682700_gfz135-B16","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1172\/JCI104530","article-title":"The effect of ACTH, renin, angiotensin II, and various precursors on biosynthesis of aldosterone by adrenal slices","volume":"41","author":"Kaplan","year":"1962","journal-title":"J Clin Invest"},{"key":"2020110509411682700_gfz135-B17","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1016\/S0021-9258(18)52235-3","article-title":"Regulation of rat adrenal messenger RNA and protein levels for cytochrome P-450s and adrenodoxin by dietary sodium depletion or potassium intake","volume":"266","author":"Tremblay","year":"1991","journal-title":"J Biol Chem"},{"key":"2020110509411682700_gfz135-B18","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0022-4731(83)90091-2","article-title":"Angiotensin II potentiates ACTH-stimulated adrenal androgen secretion","volume":"18","author":"Parker","year":"1983","journal-title":"J Steroid Biochem"},{"key":"2020110509411682700_gfz135-B19","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1677\/JME-08-0112","article-title":"Role of angiotensin II-induced rapid response genes in the regulation of enzymes needed for aldosterone synthesis","volume":"42","author":"Nogueira","year":"2009","journal-title":"J Mol Endocrinol"}],"container-title":["Nephrology Dialysis Transplantation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ndt\/article-pdf\/35\/11\/1901\/34137222\/gfz135.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ndt\/article-pdf\/35\/11\/1901\/34137222\/gfz135.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T16:53:26Z","timestamp":1609865606000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ndt\/article\/35\/11\/1901\/5542606"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,1]]},"references-count":19,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,8,1]]},"published-print":{"date-parts":[[2020,11,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ndt\/gfz135","relation":{},"ISSN":["0931-0509","1460-2385"],"issn-type":[{"value":"0931-0509","type":"print"},{"value":"1460-2385","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,11]]},"published":{"date-parts":[[2019,8,1]]}}}