Titre du document / Document title

Evidence for compromised aldosterone synthase enzyme activity in preeclampsia

Auteur(s) / Author(s)

SHOJAATI Kushiar ; CAUSEVIC Maja ; KADEREIT Bert ; DICK Bernhard ; IMOBERSTEG Jeanine ; SCHNEIDER Henning ; BEINDER Ernst ; KASHIWAGI Maki ; FREY Brigitte M. ; FREY Felix J. ; MOHAUPT Markus G. ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

Division of Nephrology/Hypertension, University of Berne, Berne, SUISSE
Women's Hospital, University of Berne, Berne, SUISSE
Women's Hospital, University of Zurich, SUISSE

Résumé / Abstract

Background. In normal pregnancy, an increased aldosterone (Aldo) concentration coincides with volume expansion. In preeclampsia, Aldo levels are low despite intravascular volume depletion. The present investigation aimed to characterize the compromised Aldo synthesis in preeclampsia, and to identify the molecular basis hereof. Methods. We recruited 66 pregnant women (24 uneventful, 42 preeclamptic). Genomic DNA was isolated from peripheral blood leukocytes. Urine samples were obtained for gas chromatography-mass spectroscopic measurements of steroid hormones reflecting apparent Aldo synthase (CYP11B2) and 11-hydroxylase (CYP11B1) activities. Polymerase chain reaction (PCR)-based screening for CYP11B2 mutations was performed by SSCP, restriction analysis, and sequencing. Results. CYP11B1 activity was unaltered, but reduction of mean tetrahydro (TH)-Aldo excretion by a factor of 3.9 indicated a diminished CYP11B2 activity in preeclampsia. Accordingly, the ratios of (TH-11-dehydrocorticosterone [A]+TH-corticosterone [B]+5α-THB) to (TH-cortisone +TH-cortisol [F]+5α-THF) and of 18-OH-THA to THAldo were increased in preeclampsia 2.6- and 15.2-fold, respectively, indicating reduced Aldo synthesis due to diminished methyl oxidase (MO) activity. A lower percentage of women with normal pregnancies had CYP11B2 mutations when compared to preeclamptic women (P < 0.05). Eight polymorphisms were detected, two of which were non-amino acid conserving. Of those, the mutation V386A, earlier found to jeopardize MO activity, was exclusively observed in preeclampsia (0% vs. 17%; P < 0.05). Conclusion. Aldo deficiency due to a compromised MO step of Aldo synthesis favors extracellular volume depletion, and may account for an increased risk of placental hypoperfusion and consecutive development of preeclampsia. The sole presence of mutation V386A in preeclamptic mothers may identify a subgroup with an increased risk to develop preeclampsia during pregnancy.

Revue / Journal Title

Kidney international   ISSN 0085-2538   CODEN KDYIA5 

Source / Source

2004, vol. 66, n^o6, pp. 2322-2328 [7 page(s) (article)] (46 ref.)

Langue / Language

Anglais

Editeur / Publisher

Nature Publishing, New York, NY, ETATS-UNIS  (1972) (Revue)

Mots-clés anglais / English Keywords

Cardiovascular disease ; Blood vessel ; Circulatory system ; Pregnancy toxemia ; Pregnancy disorders ; Steroid hormone ; Mineralocorticoid ; Adrenal hormone ; Enzyme ; Nephrology ; Urology ; Genetics ; Mutation ; Hypertension ; Artery ; Preeclampsia ; Enzymatic activity ; Synthase ; Aldosterone ;

Mots-clés français / French Keywords

Appareil circulatoire pathologie ; Vaisseau sanguin ; Appareil circulatoire ; Toxémie gravidique ; Gestation pathologie ; Hormone stéroïde ; Minéralocorticoïde ; Hormone surrénalienne ; Enzyme ; Néphrologie ; Urologie ; Génétique ; Mutation ; Hypertension artérielle ; Artère ; Prééclampsie ; Activité enzymatique ; Synthase ; Aldostérone ;

Mots-clés espagnols / Spanish Keywords

Aparato circulatorio patología ; Vaso sanguíneo ; Aparato circulatorio ; Toxemia gravídica ; Gestación patología ; Hormona esteroide ; Mineralocorticoide ; Hormona suprarrenal ; Enzima ; Nefrología ; Urología ; Genética ; Mutación ; Hipertensión arterial ; Arteria ; Preeclampsia ; Actividad enzimática ; Synthase ; Aldosterona ;

Mots-clés d'auteur / Author Keywords

aldosterone synthase ; preeclampsia ; aldosterone ; arterial hypertension ; mutation ;

Localisation / Location

INIST-CNRS, Cote INIST : 15906, 35400012129335.0230