Metabolism of MF in Inhα/Tag TG mice and proliferation of KK-1 cells with MF, P4 or MF metabolite treatment.
Serum concentrations (mean ± SEM) of MF and its metabolites following single injections of 1 mg (a) or 10 mg (b) of MF in Inhα/Tag TG mice. Effects of MF (c), P4 (d) and the 22-hydroxy, N-demethyl and Di-demethyl MF metabolites treatments (e) on KK-1 cell proliferation. Light microscopy images of cells after 5 μM or 17.5 μM MF treatment (f). Immunolocalization of HMGB1 protein after 5 μM or 17.5 μM MF treatment (g). The proliferation level of the treated groups is presented as the percentage of control proliferation, considered as 100%. Asterisks indicate significant differences between the control and treated groups (*, P < .05; **, P < .01; ***, P < .001; ****, P < .0001) (One-way ANOVA with the post-hoc Bonferroni's test). Scale bar, 20 μm. Di-demethyl MF, (11β,17β)-11-(4-Aminophenyl)-17-hydroxy-17-(1-propyn-1-yl)-estra-4,9-dien-3-one; 22-hydroxy MF, (11β,17β)-11-[4-(Dimethylamino)phenyl]-17-hydroxy-17-(3-hydroxy-1-propyn-1-yl)-estra-4,9-dien-3-one; Inhα/Tag mice; transgenic mice expressing the SV40 Taq oncogene under the inhibin α promoter; MF, mifepristone; N-demethyl MF, (11β,17β)-17-Hydroxy-11-[4-(methylamino)phenyl]-17-(1-propyn-1-yl)-estra-4,9-dien-3-one; P4, progesterone.