title: Growth Hormone Ameliorates the Radiotherapy-Induced Ovarian Follicular Loss in Rats: Impact on Oxidative Stress, Apoptosis and IGF-1/IGF-1R Axis.
abstract: 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.
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt 11566.
authors.forename: Yasmen F
authors.initials: YF
authors.lastname: Mahran
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt 11566.
authors.forename: Ebtehal
authors.initials: E
authors.lastname: El-Demerdash
authors.affiliation: National Center for Radiation Research and Technology (NCRRT), Atomic Energy Authority, Cairo, Egypt 113701.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Nada
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt 11566.
authors.forename: Reem N
authors.initials: RN
authors.lastname: El-Naga
authors.affiliation: Department of Pharmacology & Toxicology, Faulty of Pharmacy, Al-Azhar University, Cairo, Egypt 11787.
authors.forename: Azza A
authors.initials: AA
authors.lastname: Ali
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt 11566.
authors.forename: Ashraf B
authors.initials: AB
authors.lastname: Abdel-Naim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015415:Biomarkers; D001835:Body Weight; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D013006:Growth Hormone / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009929:Organ Size; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D011832:Radiation Injuries; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1