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.

Long non‑coding RNA HOTAIR overexpression improves premature ovarian failure by upregulating Notch‑1 expression

“…HOTAIR overexpression inhibits the apoptosis of hamster ovarian cells. Notch-1 overexpression has been reported to inhibit the apoptosis of various cancers, while activation of Notch-1 signaling has been demonstrated to be an effective treatment for premature ovarian failure (13). In the present study, HOTAIR overexpression significantly inhibited the apoptosis of hamster ovarian cells compared with control cells (P<0.05; Fig.…”

“…The results of a previous study revealed that activation of the Notch-1 signaling pathway is important for the recovery of premature ovarian failure in mice (13). It is also well known that HOTAIR interacts with the Notch pathway to exert its biological functions (19).…”

Transcriptional and histological alterations in gonad of adult zebrafish after exposure to the synthetic progestin norgestrel

“…The low expression of inl3 supported this hypothesis. Previous studies provided evidence for our hypothesis . For instance, growth hormone promoted oocyte maturation via activation of the notch signaling pathway in ovarian tissue .…”

“…Previous studies provided evidence for our hypothesis . For instance, growth hormone promoted oocyte maturation via activation of the notch signaling pathway in ovarian tissue . The notch pathway was activated during spermatogenesis in the mouse .…”

“…Previous studies reported that imbalance of notch signaling leads to an erroneous cell cycle . Moreover, growth hormone promoted oocyte maturation via activation of the notch signaling pathway in ovarian tissue . Thus, we hypothesize that increased notch signaling alters gonadal maturity stages.…”