Estimation of the Mechanism of Adrenal Action of Endocrine-Disrupting Compounds Using a Computational Model of Adrenal Steroidogenesis in NCI-H295R Cells

Figure 6

Heat-map of the global dynamic sensitivity analysis of adrenal steroid concentrations produced by NCI-H295R cells. The global dynamic sensitivity analysis is a powerful tool to comprehensively understand the dependencies of the model parameters in the mathematical model of the biological complex system. Dynamic sensitivities of model parameters in the mathematical model of adrenal steroidogenesis in NCI-H295R cells were calculated for all steroid concentrations in the culture medium every 6 h until 72 h after stimulation. To clarify the view of heat-map of global dynamic sensitivity analysis, imaginary data of the dynamics of steroid concentrations in the original model (blue line) and perturbed model for sensitivity analysis (red line) were prepared (a). Using this imaginary data, the calculated dynamic sensitivities (b) and the visualized dynamic sensitivity as one block of the heat-map (c) were shown, respectively. By the same method that explained using imaginary data, the large-scale data of the global dynamic sensitivity analysis on the mathematical model of adrenal steroidogenesis in NCI-H295R cells was comprehensively visualized as a big graph of heat-map (d). Parameter numbers in the horizontal axis are (1) , (2) , (3) , (4) , (5) , (6) , (7) , (8) , (9) , (10) , (11) , (12) , (13) , (14) , (15) , (16) , (17) , (18) , (19) , (20) , (21) , (22) , (23) , (24) , (25) , (26) , (27) , (28) , (29) , (30) , (31) , (32) , (33) , (34) , (35) , (36) , (37) , (38) , (39) , (40) , (41) , and (42) . PREG: pregnenolone, HPREG: 17α-hydroxypregnenolone, DHEA: dehydroepiandrosterone, PROG: progesterone, HPROG: 17α-hydroxyprogesterone, DIONE: androstenedione, DCORTICO: 11-deoxycorticosterone, DCORT: 11-deoxycortisol, CORTICO: corticosterone, CORT: cortisol, ALDO: aldosterone, and TESTO: testosterone.

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