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

Figure 7

Metabolic categories of the steroidogenic cells determined by the balance of HSD3B2 and CYP17H activities. The two-dimensional parameter scanning analysis by the perturbation of two focused parameters clarifies the interaction and the relationship between the two parameters in the complex system. Functional cellular categories of steroidogenic cells were defined by the levels of mineralocorticoid (ALDO), glucocorticoids (DCORT and CORT), and androgens (DHEA and DIONE) at 72 h after stimulation. Enzymatic activities of HSD3B2 and CYP17 were normalized by standard values of the simulation model in NCI-H295R cells. Scanning ranges of HSD3B2 and CYP17 activities were 0–200%, each 10%. Green regions are all 14 steroids produced by NCI-H295R cells. Red, blue, and purple regions are mineralocorticoid producing cells, glucocorticoids-producing cells, and both corticoid-producing cells, respectively. Yellow regions are steroidogenesis of NCI-H295R cells terminated upstream of the adrenal steroidogenesis pathway.