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

Figure 1

Schematic diagram of the mathematical model of adrenal steroidogenesis in NCI-H295R cells. Overview of the mathematical model of adrenal steroidogenesis in NCI-H295R cells, including cholesterol transport and intracellular localization, oxysterol synthesis, the C₂₁-steroid hormone biosynthesis pathway, passive diffusional transport of steroid hormones, and cell proliferation. CHOL: total cholesterol in medium culture, CHOS: stored cholesterol esters in the endoplasmic reticulum, CHOC: intracellular free cholesterol, CHOM: mitochondrial free cholesterol, CHON: mitochondrial free cholesterol close to CYP11A1 enzymes, CHOR: mitochondrial free cholesterol remote from CYP11A1 enzymes, 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, TESTO: testosterone, E1: estrone, E2: 17β-estradiol, OXY: oxysterol, CEH: cholesterol ester hydrolase, StAR: steroidogenic acute regulatory protein, CYP11A1: P450 side chain cleavage enzyme, CYP17H: 17α-hydroxylase of CYP17, CYP17L: lyase of CYP17, HSD3B2: 3β-hydroxysteroid dehydrogenase, CYP21A2: 21-hydroxylase, CYP11B1: 11β-hydroxylase, CYP11B2: 18-hydroxylase, HSD17B3: 17β-hydroxysteroid dehydrogenase, and CYP19A1: aromatase.