Mahran Yasmen F, El-Demerdash Ebtehal, Nada Ahmed S, El-Naga Reem N, Ali Azza A, Abdel-Naim Ashraf B
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt 11566.
National Center for Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo, Egypt 113701.
PLoS One. 2015 Oct 14;10(10):e0140055. doi: 10.1371/journal.pone.0140055. eCollection 2015.
Radiotherapy is one of the standard cytotoxic therapies for cancer. However, it has a profound impact on ovarian function leading to premature ovarian failure and infertility. Since none of the currently available methods for fertility preservation guarantees future fertility, the need for an effective radioprotective agent is highly intensified. The present study investigated the mechanisms of the potential radioprotective effect of growth hormone (GH) on γ irradiation-induced ovarian failure and the impact of the insulin like growth factor 1 (IGF-1) in the underlying protection. Immature female Sprague-Dawley rats were either exposed to single whole body irradiation (3.2 Gy) and/or treated with GH (1 mg/kg s.c). Experimental γ-irradiation produced an array of ovarian dysfunction that was evident by assessment of hormonal changes, follicular development, proliferation marker (PCNA), oxidative stress as well as apoptotic markers. In addition, IGF-1/IGF-1R axis expression was assessed using real-time PCR and immunolocalization techniques. Furthermore, after full maturity, fertility assessment was performed. GH significantly enhanced follicular development and restored anti-Mullerian hormone serum level as compared with the irradiated group. In addition, GH significantly ameliorated the deleterious effects of irradiation on oxidative status, PCNA and apoptosis. Interestingly, GH was shown to enhance the ovarian IGF-1 at transcription and translation levels, a property that contributes significantly to its radioprotective effect. Finally, GH regained the fertility that was lost following irradiation. In conclusion, GH showed a radioprotective effect and rescued the ovarian reserve through increasing local IGF-1 level and counteracting the oxidative stress-mediated apoptosis.
放射治疗是癌症的标准细胞毒性疗法之一。然而，它对卵巢功能有深远影响，会导致卵巢早衰和不孕。由于目前现有的任何生育力保存方法都不能保证未来的生育能力，因此对有效放射防护剂的需求变得极为迫切。本研究调查了生长激素（GH）对γ射线诱导的卵巢功能衰竭的潜在放射防护作用机制，以及胰岛素样生长因子1（IGF-1）在潜在保护作用中的影响。将未成熟的雌性斯普拉格-道利大鼠暴露于单次全身照射（3.2 Gy）和/或用GH（1 mg/kg皮下注射）进行治疗。通过评估激素变化、卵泡发育、增殖标志物（PCNA）、氧化应激以及凋亡标志物，实验性γ射线照射产生了一系列卵巢功能障碍。此外，使用实时PCR和免疫定位技术评估IGF-1/IGF-1R轴的表达。此外，在大鼠完全成熟后进行生育力评估。与照射组相比，GH显著促进了卵泡发育并恢复了抗苗勒管激素血清水平。此外，GH显著改善了照射对氧化状态、PCNA和凋亡的有害影响。有趣的是，GH在转录和翻译水平上均能增强卵巢IGF-1，这一特性对其放射防护作用有显著贡献。最后，GH恢复了照射后丧失的生育能力。总之，GH显示出放射防护作用，并通过提高局部IGF-1水平和对抗氧化应激介导的凋亡来挽救卵巢储备。
