Influence of 17-hydroxyprogesterone, progesterone and sex steroids on mineralocorticoid receptor transactivation in congenital adrenal hyperplasia
Author(s)
Type
Journal Article
Abstract
Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency leads to accumulation of steroid precursors and adrenal androgens. These steroids may have a biological effect on the steroid receptor with clinical consequences on diagnostics and treatment in CAH patients. Therefore, we analysed the effect of accumulated steroids [17-hydroxyprogesterone (17OHP), progesterone, androstenedione and testosterone] on aldosterone-mediated transactivation of the human mineralocorticoid receptor (hMR). Methods: A transactivation assay using transiently transfected COS7 cells was employed. Cells were co-transfected with hMR-cDNA, MMTV-luciferase and renilla-luciferase expression vectors. Transfected cells were incubated with six different steroid concentrations in addition to aldosterone (10-10M). Luciferase and renilla activities were measured to quantify hMR transactivation. Results: Linear regression analysis showed statistically significant linear inhibition of transactivation of the hMR by 10-10M aldosterone in the presence of increasing 17OHP [F(1,5) = 11.34, p = 0.019] and progesterone [F(1,5) = 11.08, p = 0.021] concentrations. In contrast, neither androstenedione nor testosterone affected hMR transactivation by aldosterone at a concentration of 10-10M. Conclusion: Our study shows for the first time that neither androstenedione nor testosterone has a biological effect on aldosterone-mediated transactivation of the hMR. 17OHP and progesterone have an anti-mineralocorticoid effect in vitro that may clinically lead to an increased requirement of mineralocorticoids in poorly controlled CAH patients.
Date Issued
2015-07-01
Date Acceptance
2015-01-02
Citation
Hormone Research in Paediatrics, 2015, 83 (6), pp.414-421
ISSN
1663-2818
Publisher
Karger Publishers
Start Page
414
End Page
421
Journal / Book Title
Hormone Research in Paediatrics
Volume
83
Issue
6
Copyright Statement
© 2015 S. Karger AG, Basel
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/25896481
PII: 000374112
Subjects
17-hydroxyprogesterone
21-HYDROXYLASE DEFICIENCY
CELLS
Congenital adrenal hyperplasia
Endocrinology & Metabolism
GLUCOCORTICOID-RECEPTOR
HYPERTENSION
IMMUNOLOCALIZATION
Life Sciences & Biomedicine
LOCALIZATION
Mineralocorticoid receptor
MUTATION
Pediatrics
POLYMORPHISM
Progesterone
Science & Technology
Sex steroids
TESTOSTERONE
Publication Status
Published
Coverage Spatial
Switzerland
Date Publish Online
2015-04-15