An antioxidant drug, silibinin, modulates steroid secretion in human pathological adrenocortical cells

Because human adrenocortical cells from different adrenal disorders exhibit pathologically altered corticosteroid synthesis, and free radical mechanisms may induce pathological changes in the activities of corticosteroid biosynthetic enzymes (cytochrome P-450), we examined the effect of an antioxidant, silibinin, on basal and ACTH-stimulated secretion of several corticosteroids in isolated adrenal cells from an aldosterone-producing adenoma, atrophied adrenal tissues surrounding the adenoma, and hyperplastic adrenals from Cushing's syndrome. In the presence of a high concentration (100 mumol/l) of silibinin, variably diminished secretion of basal aldosterone, corticosterone, cortisol, 18-OH-corticosterone and 11-deoxycorticosterone was found. In contrast, the addition of 0.01 mumol silibinin/l, which failed to produce a clear effect on basal corticosteroid secretion, resulted in a potentiation of ACTH-stimulated secretion of several corticosteroids in the adenomatous and hyperplastic adrenocortical cells. These results suggest that the dose-dependent dual effect of silibinin on corticosteroid secretion may be attributed to corresponding changes in the activities of cytochrome P-450 enzymes, and that stimulation of ACTH-induced corticosteroidogenesis by silibinin is presumably due to the antioxidant property of the drug.