Growth hormone treatment of premature ovarian failure in a mouse model via stimulation of the Notch-1 signaling pathway

Liu,Te; Wang,Suwei; Zhang,Lina; Guo,Lihe; Yu,Zhihua; Chen,Chuan; Zheng,Jin

doi:10.3892/etm.2016.3326

Growth hormone treatment of premature ovarian failure in a mouse model via stimulation of the Notch-1 signaling pathway

Authors:
- Te Liu
- Suwei Wang
- Lina Zhang
- Lihe Guo
- Zhihua Yu
- Chuan Chen
- Jin Zheng
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Affiliations: Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China, Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China
Published online on: May 10, 2016 https://doi.org/10.3892/etm.2016.3326
Pages: 215-221
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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