title: Growth hormone treatment of premature ovarian failure in a mouse model via stimulation of the Notch-1 signaling pathway.
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.
authors.affiliation: 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.
authors.forename: T E
authors.initials: TE
authors.lastname: Liu
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Suwei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
authors.forename: Lihe
authors.initials: L
authors.lastname: Guo
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Gynecology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zheng
keywords: growth hormone; hormone therapy; mouse model of disease; notch-1 signaling pathway; premature ovarian failure