Fig. 4

Effects of Osilodrostat inhibition on classic steroidogenesis in human fetal adrenals. Effects of Osilodrostat (1 μM) on HFA tissue cultured ex vivo for 14 days under basal and ACTH-stimulated conditions. a Quantification of androgens, glucocorticoids, and steroidogenic intermediate concentrations presented as a ratio relative to the mean of vehicle controls (indicated by dotted lines). b Affected enzyme activity reflected by CYP11B1/2 product/substrate ratios of measured steroids relative to the mean of vehicle controls. c Affected CYP11B1/2 enzyme activity reflected by ratios representing changes in androstenedione/corticosteroids downstream of the mineralocorticoid (corticosterone) and glucocorticoid (cortisol) pathways. Media was pooled from 1 to 13 tissue fragments per treatment depending on the initial size of half of the adrenal gland. Values represent geometric mean with 95% CI, n = 10 (fetuses). Significant difference compared with vehicle controls from the same fetus were based on ln-transformed data using repeated measures one-way ANOVA followed by Tukey’s multiple comparisons test. (*) indicate differences compared with vehicle controls, (¤) indicate differences compared with ACTH treatment. *^/¤p < 0.05, **^/¤¤p < 0.01, ***^/¤¤¤p < 0.001, ****^/¤¤¤¤P < 0.0001. DHEAS, dehydroepiandrosterone-sulfate