LHRH Antagonist Cetrorelix In The Treatment Of Benign Prostatichyperplasia:an Experimental Study In Rats

Part1The Establishment and Evaluation of a Rat Model of Benign Prostatic HyperplasiaObjective:to establish a effective and reliable rat model of benign prostatic hyperplasia, which laid the foundation for a subsequent experiments.Methods:BPH model of SD rats were induced by daily subcutaneous injection in the right flank of testosterone propionate (TP;2mg/d). Prostate weight and prostate size were assessed in different modeling time, and proliferation of prostatic epithelial cells and stromal cells was investigated by H&E stain in order to identify the best modeling time and the reliability of the model.Results:The wet weight and size of model prostates were conspicuously increased by subcutaneous injection of testosterone propionate. The best cycle time of the model is4weeks, and proliferation of prostatic epithelial cells and stromal cells was obvious in H&E stain.Conclusion:We can use2mg/d testosterone propionate subcutaneous injection for4weeks to build a rat model of BPH. This is simple and reliable method to establish a rat BPH model. Part2Histomorphology Study of LHRH Antagonist Cetrorelix Treatment of Benign Prostatic hyperplasia in a Rat ModelObjective:to explore the changes after LHRH antagonist Cetrorelix treatment of benign prostatic hyperplasia in rat, and observe the apoptosis in the prostate.Methods:Different doses of LHRH antagonist Cetrorelix were injected into the BPH rat model on days1,8and15after BPH induction. We harvested the prostate on days22, then got the weight and size of prostate and observed the apoptosis of prostatic cells by TUNEL assay.Results:After treatment with different doses of Cetrorelix, the wet weight and volume of the prostate had decreased sharply. The wet weight of prostate has decreased from1.010±0.111g in the control group to0.856±0.053g in the low-dose Cetrorelix group (P<0.05), and further decrease occurred with Cetrorelix at a high dose. The volume has decreased from0.966±0.086ml in the control group to0.649±0.040ml in the high-dose Cetrorelix group(P<0.05). The TUNEL staining indicated that treatment with different doses of Cetrorelix may lead cell apoptosis in the prostate of the rat model. The apoptosis index of the high-dose Cetrorelix group was0.710±0.061, compared to0.025±0.005in the control group.Conclusion:LHRH antagonist Cetrorelix can induce the cell apoptosis of the prostatic in a rat model of BPH, which leads to the decrease of the prostate weight and size. Part3Mechanisms of Prostate Atrophy after LHRH Antagonist Cetrorelix Injection in a Rat Model of Benign Prostatic HyperplasiaObjective:Previous studies have proved that luteinizing hormone-releasing hormone antagonist Cetrorelix significantly improves the symptoms of benign prostatic hyperplasia (BPH) and reduces gland size. Transforming growth factor-P (TGF-β) plays an important role in regulating the growth of prostatic cells, in which it inhibits cellular proliferation while promotes apoptosis. In the present study, we investigated the roles of TGF-β signaling pathway in a rat BPH mode treated with Cetrorelix.Methods:After BPH induction, the rats were randomly divided into four groups of ten animals each, then experimental groups received the following treatment:Group A, Nothing; Group B, distilled water; Group C, Cetrorelix0.71mg/kg; Group D, Cetrorelix3.55mg/kg. Group B, C, D animals were administered subcutaneous injections in the left flank on days1,8and15after BPH induction; Group A animals were injected nothing on the same schedule. Rats were sacrificed under anesthesia on the morning of day22. The proximal and distal regions were snap frozen for mRNA determination and protein analysis. TGF-β1and c-Myc expression were measured by qRT-PCR and western blot in the proximal region and the distal region of ventral prostatic lobes, respectively.Results:The mRNA level of TGF-β1in the proximal part of prostate was significantly upregulated in the Cetrorelix group (P＜O.05), while the mRNA level of c-Myc was significantly remarkably downregulated (P＜O.05) in the proximal part of prostate; the changes in the TGF-β1and c-Myc protein levels were similar to the mRNA responses by treatment with Cetrorelix in the proximal part of prostate. Conclusion:TGF-β signaling pathway plays a role in BPH treated with Cetrorelix. Our findings suggest that the TGF-β signaling pathways may be one of the major reasons for prostate volume reduction in BPH rats after Cetrorelix treatment.