Model schematic and metabolism of deuterium-labeled glucocorticoids. (a) Model schematic showing the three compartments (maternal, syncytiotrophoblast, and fetal) distinguished in the model. It is assumed that transfer between compartments is by simple diffusion, whereas metabolic conversion between cortisol and cortisone takes place in the syncytiotrophoblast (equations 1 to 6, see “Methods” section). The input concentration of D4-cortisol in the maternal compartment varies over time according to the experimental protocol, whereas the input concentration in the fetal compartment is zero at all times. The output concentrations of the maternal and fetal compartments from the model can be compared with the experimental data. D4-Cortisol is inactivated by 11β-HSD2 to D3-cortisone, with the loss of the deuterium on C11. (b) 11β-HSD1 regenerates D3-cortisol from D3-cortisone, with the addition of an unlabeled hydrogen.