title: An antioxidant drug, silibinin, modulates steroid secretion in human pathological adrenocortical cells.
abstract: 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.
authors.affiliation: Second Department of Medicine, Semmelweis University Medical School, Budapest, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Rácz
authors.forename: J
authors.initials: J
authors.lastname: Fehér
authors.forename: G
authors.initials: G
authors.lastname: Csomós
authors.forename: I
authors.initials: I
authors.lastname: Varga
authors.forename: R
authors.initials: R
authors.lastname: Kiss
authors.forename: E
authors.initials: E
authors.lastname: Gláz
mesh_terms: D015069:18-Hydroxycorticosterone / Q000378:metabolism; D000236:Adenoma / Q000503:physiopathology; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000303:Adrenal Cortex Diseases / Q000503:physiopathology*; D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms / Q000503:physiopathology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D003345:Corticosterone / Q000378:metabolism; D003900:Desoxycorticosterone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D012838:Silymarin / Q000494:pharmacology*; D013268:Stimulation, Chemical
chemical_list: D000305:Adrenal Cortex Hormones; D000975:Antioxidants; D005419:Flavonoids; D012838:Silymarin; D003900:Desoxycorticosterone; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D006854:Hydrocortisone