title: Influence of 17-Hydroxyprogesterone, Progesterone and Sex Steroids on Mineralocorticoid Receptor Transactivation in Congenital Adrenal Hyperplasia.
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.
  
  
  CONCLUSIONS
  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. © 2015 S. Karger AG, Basel.
authors.affiliation: Centre for Endocrinology, Diabetes, and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Christiaan F
authors.initials: CF
authors.lastname: Mooij
authors.forename: Silvia
authors.initials: S
authors.lastname: Parajes
authors.forename: Karijn J
authors.initials: KJ
authors.lastname: Pijnenburg-Kleizen
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
authors.forename: Nils
authors.initials: N
authors.lastname: Krone
authors.forename: Hedi L
authors.initials: HL
authors.lastname: Claahsen-van der Grinten