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.
Highlights
Radiotherapy is one of the most effective cytotoxic therapies for cancer [1]
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
The results demonstrated a modest degree of IGF-1 receptor (IGF-1R) expression in ovaries of both the control and GH groups (Fig 6A & 6D), with no significant difference between them (Fig 6E)
Summary
Radiotherapy is one of the most effective cytotoxic therapies for cancer [1]. About eighty percent of cancer patients need radiotherapy at some time or other [2]. Normal tissues adjacent to the tumor are unavoidably exposed to radiation and reduce its therapeutic gain [1] Physicians viewed these drastic effects as an acceptable cost of curative radiotherapy [3, 4]. The ovaries are exposed to significant doses of irradiation when radiotherapy is used to treat pelvic and abdominal diseases or through the whole body irradiation [6]. In this context, radiation to the brain can damage the pituitary gland, leading to deregulation of the two gonadotropins [follicle stimulating hormone (FSH) and luteinizing hormone (LH)] required to maintain normal ovarian function [7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
