Effects of excess corticosterone on NADPH generating enzymes and glucose oxidation in Leydig cells of adult rats

Abstract

Clinical and experimental studies have shown the adverse effects of excess glucocorticoid on testicular testosterone production. The NADPH co-enzyme has been recognized as an important factor that regulates several steps in steroidogenesis, while glucose oxidation acts as a limiting factor on testicular testosterone production. Nevertheless, the impact of excess corticosterone, the stress hormone on testicular NADPH availability and glucose oxidation is unknown. Therefore, the present study was designed to assess the specific effects of excess corticosterone on Leydig cell NADPH generating enzymes and glucose oxidation. Adult Wistar rats (200–250 g, b.w.) were treated with corticosterone-21-acetate (2 mg/100 g, b.w., i.m., twice daily) for 10 days and corticosterone-21-acetate plus luteinizing hormone (LH) (100 mg/kg b.w., i.m., daily) for 10 days. After the treatment period, experimental animals and controls were killed, blood was collected and the sera separated for testosterone assay. Testes were removed and Leydig cells were isolated, purified and used for estimating the specific activity of NADPH generating enzymes and ¹⁴C-glucose oxidation. Serum testosterone, Leydig cellular ¹⁴C-glucose oxidation and the specific activities of 6-phosphogluconate dehydrogenase (6-PGDH), NADP-iso-citrate dehydrogenase (ICDH) and malic enzyme were significantly decreased in corticosterone-treated rats. Coadministration of LH with corticosterone maintained the specific activities of 6-PGDH and ICDH and ¹⁴C-glucose oxidation at control level. Nevertheless, serum testosterone and Leydig cellular malic enzyme activity showed a significant decrease in these rats. In conclusion, the inhibitory effects of excess corticosterone on Leydig cell steroidogenesis are mediated through impaired glucose oxidation and defective NADPH generation. Co-administration of LH with corticosterone failed to prevent the decrease in serum testosterone and Leydig cell malic enzyme activity, suggesting the dominant inhibitory effects of excess corticosterone.

Keywords

corticosterone 14C-glucose oxidation Leydig cell LH NADPH generation

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