Abstract：
BACKGROUND: Despite the high number of synthetic androgenic-anabolic steroids, testosterone is still misused for doping in amateur and professional sports. However, only few studies investigated the dose-response effects of testosterone beyond its physiological concentrations and in over 90 years of research, no saturation dosage has been experimentally described for exogenous testosterone administration.
OBJECTIVE: We want to elucidate the physiological and pathophysiological effects of supra-physiological testosterone application and close this gap in testosterone dose-response data.
METHODS: Male orchiectomized rats were treated with different testosterone doses ranging from 0.1 to 50 mg/kg body weight for 3 weeks. Several physiological endpoints (e.g., body weight, organ and muscle weight, muscle strength, muscle fiber size) were examined during and after the termination of the treatment with an adjusted Hershberger assay, open-field-test, and (immuno-)histologic.
RESULTS: The wet weights of androgen responsive organs (penis, prostate, seminal vesicle) showed a significant increase in a dose-dependent manner. Histological evaluation of the prostate showed a significant higher percentage of KI67 positive prostate nuclei in the highest dosage group and an increasing hyperplasia with increasing testosterone administered. A significant anabolic effect was only observed in Levator ani wet weight, and to minor degree for the cardiac muscle. Regarding other skeletal muscles (Musculus soleus and Musculus gastrognemicus), no significant testosterone effects were observed. We showed a significant increasing dosage-response effect for testosterone in androgen responsive organs with saturation at the two highest concentration of 10 and 50 mg/kg body weight.
CONCLUSIONS: The dose-dependent androgenic effects of testosterone were well observable and the anabolic effects on muscle tissue were visible although to a lesser degree, without the support of aerobic exercise and a protein rich diet. Future studies should investigate a combinatorial effect of testosterone and training. Nevertheless, with the chosen range of applied testosterone, we showed a saturation of testosterone effects in prostate, seminal vesicle, penis, and Levator ani.
OBJECTIVE: We want to elucidate the physiological and pathophysiological effects of supra-physiological testosterone application and close this gap in testosterone dose-response data.
METHODS: Male orchiectomized rats were treated with different testosterone doses ranging from 0.1 to 50 mg/kg body weight for 3 weeks. Several physiological endpoints (e.g., body weight, organ and muscle weight, muscle strength, muscle fiber size) were examined during and after the termination of the treatment with an adjusted Hershberger assay, open-field-test, and (immuno-)histologic.
RESULTS: The wet weights of androgen responsive organs (penis, prostate, seminal vesicle) showed a significant increase in a dose-dependent manner. Histological evaluation of the prostate showed a significant higher percentage of KI67 positive prostate nuclei in the highest dosage group and an increasing hyperplasia with increasing testosterone administered. A significant anabolic effect was only observed in Levator ani wet weight, and to minor degree for the cardiac muscle. Regarding other skeletal muscles (Musculus soleus and Musculus gastrognemicus), no significant testosterone effects were observed. We showed a significant increasing dosage-response effect for testosterone in androgen responsive organs with saturation at the two highest concentration of 10 and 50 mg/kg body weight.
CONCLUSIONS: The dose-dependent androgenic effects of testosterone were well observable and the anabolic effects on muscle tissue were visible although to a lesser degree, without the support of aerobic exercise and a protein rich diet. Future studies should investigate a combinatorial effect of testosterone and training. Nevertheless, with the chosen range of applied testosterone, we showed a saturation of testosterone effects in prostate, seminal vesicle, penis, and Levator ani.
摘要：
背景：尽管合成雄激素合成类固醇的数量很多，睾丸激素仍然被滥用于业余和职业运动中的兴奋剂。然而,在超过90年的研究中，只有少数研究调查了睾酮超过其生理浓度的剂量效应，对于外源性睾酮给药，没有实验描述饱和剂量。
目的：我们希望阐明超生理睾酮应用的生理和病理生理效应，并缩小睾酮剂量效应数据的差距。
方法：用0.1至50mg/kg体重的不同睾酮剂量治疗雄性睾丸切除大鼠3周。几个生理终点(例如，体重,器官和肌肉重量，肌肉力量,肌肉纤维大小）在治疗终止期间和之后用调整后的Hershberger测定法进行检查，开场试验,和（免疫）组织学。
结果：雄激素反应器官的湿重（阴茎，前列腺,精囊）以剂量依赖性方式显着增加。前列腺的组织学评估显示，在最高剂量组中，KI67阳性前列腺核的百分比明显更高，并且随着睾丸激素的增加，增生增加。一个显著的合成代谢作用只观察到提拔肛湿重，对心肌也有轻微的影响。关于其他骨骼肌（比目鱼肌和胃底肌），未观察到显著的睾酮效应。我们在10和50mg/kg体重的两个最高浓度下，在饱和的雄激素反应器官中，睾酮的剂量效应显着增加。
结论：睾酮的剂量依赖性雄激素效应是可观察到的，对肌肉组织的合成代谢作用是可见的，尽管程度较小，没有有氧运动和富含蛋白质的饮食的支持。未来的研究应该研究睾酮和训练的组合效应。然而，根据所选择的睾丸激素范围，我们显示了前列腺中睾酮作用的饱和，精囊,阴茎,还有Levatorani.
目的：我们希望阐明超生理睾酮应用的生理和病理生理效应，并缩小睾酮剂量效应数据的差距。
方法：用0.1至50mg/kg体重的不同睾酮剂量治疗雄性睾丸切除大鼠3周。几个生理终点(例如，体重,器官和肌肉重量，肌肉力量,肌肉纤维大小）在治疗终止期间和之后用调整后的Hershberger测定法进行检查，开场试验,和（免疫）组织学。
结果：雄激素反应器官的湿重（阴茎，前列腺,精囊）以剂量依赖性方式显着增加。前列腺的组织学评估显示，在最高剂量组中，KI67阳性前列腺核的百分比明显更高，并且随着睾丸激素的增加，增生增加。一个显著的合成代谢作用只观察到提拔肛湿重，对心肌也有轻微的影响。关于其他骨骼肌（比目鱼肌和胃底肌），未观察到显著的睾酮效应。我们在10和50mg/kg体重的两个最高浓度下，在饱和的雄激素反应器官中，睾酮的剂量效应显着增加。
结论：睾酮的剂量依赖性雄激素效应是可观察到的，对肌肉组织的合成代谢作用是可见的，尽管程度较小，没有有氧运动和富含蛋白质的饮食的支持。未来的研究应该研究睾酮和训练的组合效应。然而，根据所选择的睾丸激素范围，我们显示了前列腺中睾酮作用的饱和，精囊,阴茎,还有Levatorani.
