title: Chronic potassium depletion increases adrenal progesterone production that is necessary for efficient renal retention of potassium.
abstract: Modern dietary habits are characterized by high-sodium and low-potassium intakes, each of which was correlated with a higher risk for hypertension. In this study, we examined whether long-term variations in the intake of sodium and potassium induce lasting changes in the plasma concentration of circulating steroids by developing a mathematical model of steroidogenesis in mice. One finding of this model was that mice increase their plasma progesterone levels specifically in response to potassium depletion. This prediction was confirmed by measurements in both male mice and men. Further investigation showed that progesterone regulates renal potassium handling both in males and females under potassium restriction, independent of its role in reproduction. The increase in progesterone production by male mice was time dependent and correlated with decreased urinary potassium content. The progesterone-dependent ability to efficiently retain potassium was because of an RU486 (a progesterone receptor antagonist)-sensitive stimulation of the colonic hydrogen, potassium-ATPase (known as the non-gastric or hydrogen, potassium-ATPase type 2) in the kidney. Thus, in males, a specific progesterone concentration profile induced by chronic potassium restriction regulates potassium balance.
authors.affiliation: UPMC Univ Paris 6/INSERM/CNRS, Laboratoire de Génomique, Physiologie et Physiopathologie Rénales, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Boutaïna
authors.initials: B
authors.lastname: Elabida
authors.forename: Aurélie
authors.initials: A
authors.lastname: Edwards
authors.forename: Amel
authors.initials: A
authors.lastname: Salhi
authors.forename: Anie
authors.initials: A
authors.lastname: Azroyan
authors.forename: Heidi
authors.initials: H
authors.lastname: Fodstad
authors.forename: Pierre
authors.initials: P
authors.lastname: Meneton
authors.forename: Alain
authors.initials: A
authors.lastname: Doucet
authors.forename: May
authors.initials: M
authors.lastname: Bloch-Faure
authors.forename: Gilles
authors.initials: G
authors.lastname: Crambert
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis; D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D002908:Chronic Disease; D003345:Corticosterone / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007008:Hypokalemia / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015735:Mifepristone / Q000494:pharmacology; D008954:Models, Biological; D017419:Potassium, Dietary / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D011374:Progesterone / Q000096:biosynthesis* / Q000097:blood; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D012982:Sodium, Dietary / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D006727:Hormone Antagonists; D017419:Potassium, Dietary; D011980:Receptors, Progesterone; D012982:Sodium, Dietary; D015735:Mifepristone; D000450:Aldosterone; D011374:Progesterone; D017506:H(+)-K(+)-Exchanging ATPase; D003345:Corticosterone