C.F., Mooij S., Parajes K.J., Pijnenburg-Kleizen W., Arlt N., Krone der Grinten H.L., Claahsen-van Supplementary Material for: Influence of 17-Hydroxyprogesterone, Progesterone and Sex Steroids on Mineralocorticoid Receptor Transactivation in Congenital Adrenal Hyperplasia <b><i>Background:</i></b> 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). <b><i>Methods:</i></b> 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<sup>-10</sup>M). Luciferase and renilla activities were measured to quantify hMR transactivation. <b><i>Results:</i></b> Linear regression analysis showed statistically significant linear inhibition of transactivation of the hMR by 10<sup>-10</sup>M 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<sup>-10</sup>M. <b><i>Conclusion:</i></b> 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. Mineralocorticoid receptor;17-hydroxyprogesterone;Progesterone;Congenital adrenal hyperplasia;Sex steroids 2015-04-15
    https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Influence_of_17-Hydroxyprogesterone_Progesterone_and_Sex_Steroids_on_Mineralocorticoid_Receptor_Transactivation_in_Congenital_Adrenal_Hyperplasia/5127631
10.6084/m9.figshare.5127631.v1