Inhibitory Effects of Propylthiouracil on Corticosterone Production in Rat Zona Fasciculata-Reticularis Cells

Backgr ound and Objective: To examine the acute effects of propylthiouracil (PTU) on corticosterone release by rat adrenal Zona Fasciculata Reticularis (ZFR) cells. Materials and Methods: Male rats were infused with alkaline saline or PTU (10 mg kgG1) via right jugular catheter. The blood samples were collected at 0, 30, 60, 120, 180 and 240 min after infusion. Rat ZFR cells were treated with PTU (12 mM) in the presence or absence of adrenocorticotropic hormone (ACTH) (10G9 M). Media were collected for corticosterone RIA and cells were lysed for analyzing the protein expressions of Steroidogenic Acute Regulatory (StAR) protein and P450scc. The ZFR cells were also incubated with PTU (3-30 mM) plus trilostane (a 3ß-hydroxysteroid enzyme inhibitor, 10G6 M) or both trilostane and 25-OH-cholesterol (10G7~10G4 M) for 1 h and the concentration of pregnenolone in media was measured. Results: Propylthiouracil infusion decreased plasma corticosterone concentrations. Both basal and ACTH-stimulated corticosterone release as well as StAR protein expression in ZFR cells were attenuated by PTU treatment. The Electrophoretic Mobility Shift Assay (EMSA) results showed that the binding activity into Steroidogenic Factor-1 (SF-1) binding site was descreased by PTU. The elevated binding activity in response to ACTH treatment was diminished after PTU treatment. The pregnenolone production from ZFR cells was suppressed by PTU. Administration of PTU (10 mM) decreased Vmax by 46%. Conclusion: Propylthiouracil acutely diminished corticosterone production by affecting the early rate-limiting steps of steroidogenesis including the reduction of the enzyme activity of P450scc, and the expression of StAR protein.