The Effect Of Corticosterone On Antizyme MRNA And Protein Expression In Early Regenerating Rat Liver

Glucocorticoid is known to play important and complex roles in live regeneration, whereas its mechanisms remain to be clarified. Based on this, adult male Sprague-Dawley rats weighing 180-200g were used in this experiment to investigate the effect of corticosterone, the main glucocorticoid in rat, on antizyme mRNA and protein expression in early regenerating liver induced by partial hepatectomy (PH). Rats were randomly divided into five groups: control group (sham-adrenalectomy group), adrenalectomy group and adrenalectomy group treated with 10, 20 or 40 mg/kg body weight corticosterone. Bilateral adrenalectomies were performed on rats 3 days before PH, different doses of corticosterone blended in sesame oil was injected subcutaneously to adrenalectomized rats every 12 h, beginning 12 h before PH. Antizyme mRNA and protein levels in regenerating liver were determined by RT-PCR and Western blotting, respectively. Results were as follows:(1) In control group, antizyme mRNA expression was relatively low in intact liver (PH 0 h), but it was stimulated to a peak value at 3 h post-PH, followed by a significant decrease at 5 h, afterwards, it reached another peak at 7 h, then returned gradually to the baseline at 12 h.(2) In adrenalectomy group, 10 and 20 mg/kg body weight corticosterone-treated groups, the profiles of antizyme mRNA expression changed similarly to that in control group, without statistical significance found compared to control at each time point (P﹥0.05).(3) After 40 mg/kg adrenalectomy group corticosterone admininstration, antizyme mRNA level increased significantly(P﹤0.05 or P﹤0.01)except at 7 h compared to control, with the highest level occurring at 5 h post-PH and decreasing thereafter.(4) In control group, antizyme protein underwent concentration changes similar to the corresponding antizyme mRNA alterations. But when compared with control group, antizyme protein content in adrenalectomy group declined significantly at 5, 7, and 9 h after PH (P < 0.05).(5) Following different doses of exogenous corticosterone administration, antizyme protein levels increased after PH,peaking at 5 h, then falled gradually. Proteins were substantially induced during the whole experiment observed (P < 0.01), for instance, at 5 h post-PH antizyme protein levels in 10, 20, and 40 mg/kg adrenalectomy group corticosterone-treated groups increased by 43%, 79% and 95%, respectively, when compared with control at the same time point.Results obtained indicadate that exogenous corticosterone induces antizyme protein synthesis in a dose- dependent manner in early regenerating rat liver; 10 or 20 mg/kg body weight corticosterone has little effect on antizyme mRNA level, but high dose of corticosterone (40 mg/kg) could stimulate antizyme gene transcription.