Growth hormone treatment of premature ovarian failure in a mouse model via stimulation of the Notch-1 signaling pathway.
Growth hormone treatment of premature ovarian failure in a mouse model via stimulation of the Notch-1 signaling pathway.
复制标题
生长激素通过刺激 Notch-1 信号通路治疗小鼠卵巢早衰模型
DOI：
10.3892/etm.2016.3326
复制
发表时间：
2016-07
影响因子：
2.7
通讯作者：
Zheng J
中科院分区：
文献类型：
--
作者：
Liu TE;Wang S;Zhang L;Guo L;Yu Z;Chen C;Zheng J
卵巢早衰(POF)是一种影响1%的普通女性的疾病，在40岁之前会导致闭经、促性腺激素亢进和雌激素减少。目前，POF无法逆转，尽管有治疗方法可用，但迫切需要改进治疗策略。生长激素(GH)是一种多效性激素，影响从碳水化合物和脂肪代谢到免疫反应的广泛生理功能。在非转基因的临床前试验中，GH曾被用于治疗POF，但这些作用背后的生化机制尚不清楚。在本研究中，用环磷酰胺建立了POF小鼠模型。用重组小鼠生长激素(RmGH)处理POF小鼠，可明显减轻卵巢组织中POF的组织病理学改变，减轻卵巢颗粒细胞损伤，减少闭锁卵泡数，显著增加成熟卵母细胞数。此外，酶联免疫吸附试验显示，与POF模型组相比，中剂量rmGH(0.8 mg/kg)治疗组小鼠血浆雌二醇水平随时间延长而升高，血浆卵泡刺激素水平随时间延长而降低(P<；0.05)。此外，逆转录定量聚合酶链式反应和免疫组织化学分析显示，野生型小鼠和中、高剂量rmGH组Notch-1信号通路因子(Notch1、CBF1和HES1)水平升高，而低剂量rmGH组小鼠无此变化。结论：GH可能通过激活卵巢组织中的Notch-1信号通路，促进卵巢组织修复、雌激素释放和卵母细胞成熟。
Premature ovarian failure (POF) is a condition affecting 1% of women in the general population, causing amenorrhea, hypergonadotropism and hypoestrogenism before the age of 40. Currently, POF cannot be reversed and, although treatments are available, there is an urgent need for improved treatment strategies. Growth hormone (GH) is a pleiotropic hormone that affects a broad spectrum of physiological functions, from carbohydrate and lipid metabolism to the immune response. GH has previously been used to treat POF in non-transgenic preclinical trials, but the biochemical mechanism underlying these effects are unclear. In the present study, a mouse model of POF was generated using cyclophosphamide. Treatment of POF mice with recombinant mouse growth hormone (rmGH) was revealed to markedly reduce POF histopathology in ovarian tissue, relieve ovarian granulosa cell injury, reduce the number of atretic follicles and significantly increase the number of mature oocytes. Furthermore, an enzyme-linked immunosorbent assay revealed that plasma estradiol levels increased and plasma follicle stimulating hormone levels decreased with time in a group of mice treated with a medium dose of rmGH (0.8 mg/kg) when compared with the POF model group (P<0.05). In addition, reverse transcription-quantitative polymerase chain reaction and immunohistochemical analysis demonstrated elevated levels of Notch-1 signaling pathway factors (Notch1, CBF1, and HES1) in wild-type mice and those treated with medium and high doses of rmGH, but not in those treated with low doses of rmGH. In conclusion, GH may promote ovarian tissue repair, estrogen release and oocyte maturation via activation of the Notch-1 signaling pathway in ovarian tissue.