+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

      Disorders of the Aldosterone Synthase and Steroid 11β-Hydroxylase Deficiencies

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          The most potent corticosteroids are 11β-hydroxylated compounds. In humans, two cytochrome P450 isoenzymes with 11β-hydroxylase activity, catalysing the biosynthesis of cortisol and aldosterone, are present in the adrenal cortex. CYP11B1, the gene encoding 11β-hydroxylase (P450c11), is expressed on high levels in the zona fasciculata and is regulated by ACTH. CYP11B2, the gene encoding aldosterone synthase (P450c11Aldo), is expressed in the zona glomerulosa under primary control of the renin-angiotensin system. Aldosterone synthase has 11β-hydroxylase activity as well as 18-hydroxylase activity and 18-oxidase activity. The substrate for CYP11B2 is 11-deoxycorticosterone, that of CYP11B1 is 11-deoxycortisol. Mutations in CYP11B1 cause congenital adrenal hyperplasia (CAH) due to 11β-hydroxylase deficiency. This disorder is characterized by androgen excess and hypertension. Mutations in CYP11B2 cause congenital hypoaldosteronism (aldosterone synthase deficiency) which is characterized by life-threatening salt loss, failure to thrive, hyponatraemia and hyperkalaemia in early infancy. Both disorders have an autosomal recessive inheritance. Classical and nonclassical forms of 11β-hydroxylase deficiency can be distinguished. Studies in heterozygotes for classical 11β-hydroxylase deficiency show inconsistent results with no or only mild hormonal abnormalities (elevated plasma levels of 11-deoxycortisol after ACTH stimulation). In infants with congenital hypoaldosteronism, a comparable frequency of 18-hydroxylase deficiency (aldosterone synthase deficiency type I) and of 18-oxidase deficiency (aldosterone synthase deficiency type II) can be found. Molecular genetic studies of the CYP11B1 and CYP11B2 genes in 11β-hydroxylase deficiency or aldosterone synthase deficiency have led to the identification of several mutations. Transfection experiments showed loss of enzyme activity in vitro. In some of the patients with 18-oxidase deficiency (aldosterone synthase deficiency type II) no mutations in the CYP11B2 gene were identified. Refined methods for steroid determination are the basis for the diagnosis of inborn errors of steroidogenesis. Molecular genetic studies are complementary; on the one hand, they have practical importance for the prenatal diagnosis of virilizing CAH forms and on the other hand, they are of theoretical importance in terms of our understanding of the functioning of cytochrome P450 enzymes.

          Related collections

          Most cited references 13

          • Record: found
          • Abstract: not found
          • Article: not found

          CYP11B1 mutations causing congenital adrenal hyperplasia due to 11 beta- hydroxylase deficiency

           S Geley (1996)
            • Record: found
            • Abstract: not found
            • Article: not found

            Disorders of steroid 11 beta-hydroxylase isozymes

             P C White (1994)
              • Record: found
              • Abstract: not found
              • Article: not found

              Novel CYP11B1 Mutations in Congenital Adrenal Hyperplasia due to Steroid 11 -Hydroxylase Deficiency

               D Merke (1998)

                Author and article information

                Horm Res Paediatr
                Hormone Research in Paediatrics
                S. Karger AG
                May 1999
                02 November 1999
                : 51
                : 5
                : 211-222
                Divisions of Paediatric Endocrinology, Departments of Paediatrics, Universities of aGeneva, Switzerland and bKiel, Germany
                23374 Horm Res 1999;51:211–222
                © 1999 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 5, Tables: 1, References: 75, Pages: 12


                Comment on this article