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Published on: October 10, 2012
Insulin-like growth factor-I gene therapy reverses morphologic changes and reduces hyperprolactinemia in experimental
Gloria M Console1, Claudia B Herenu, Gisela A Camihort
1Department of Cytology, Histology & Embryology B-CICBA, National University of La Plata, La Plata, Argentina. gconsole2@gmail.com
Background:
The implementation of gene therapy for the treatment of pituitary tumors emerges as a promising complement to surgery and may have distinct advantages over radiotherapy for this type of tumors. Up to now, suicide gene therapy has been the main experimental approach explored to treat experimental pituitary tumors. In the present study we assessed the effectiveness of insulin-like growth factor I (IGF-I) gene therapy for the treatment of estrogen-induced prolactinomas in rats.
Results:
Female Sprague Dawley rats were subcutaneously implanted with silastic capsules filled with 17-beta estradiol (E2) in order to induce pituitary prolactinomas. Blood samples were taken at regular intervals in order to measure serum prolactin (PRL). As expected, serum PRL increased progressively and 23 days after implanting the E2 capsules (Experimental day 0), circulating PRL had undergone a 3-4 fold increase. On Experimental day 0 part of the E2-implanted animals received a bilateral intrapituitary injection of either an adenoviral vector expressing the gene for rat IGF-I (RAd-IGFI), or a vector (RAd-GFP) expressing the gene for green fluorescent protein (GFP). Seven days post vector injection all animals were sacrificed and their pituitaries morphometrically analyzed to evaluate changes in the lactotroph population. RAd-IGFI but not RAd-GFP, induced a significant fall in serum PRL. Furthermore, RAd-IGFI but not RAd-GFP significantly reversed the increase in lactotroph size (CS) and volume density (VD) induced by E2 treatment.
Conclusion:
We conclude that IGF-I gene therapy constitutes a potentially useful intervention for the treatment of prolactinomas and that bioactive peptide gene delivery may open novel therapeutic avenues for the treatment of pituitary tumors.
Insights
Insulin-like growth factor I (IGF-I) gene therapy effectively reduced prolactin levels and normalized pituitary tumor size in a rat model. This gene therapy approach shows promise for treating prolactinomas and other pituitary tumors.
Area of Science:
- Endocrinology
- Gene Therapy
- Oncology
Background:
- Gene therapy offers a promising alternative to traditional treatments like surgery and radiotherapy for pituitary tumors.
- Suicide gene therapy has been the primary experimental approach for pituitary tumors to date.
- This study investigates insulin-like growth factor I (IGF-I) gene therapy for estrogen-induced prolactinomas in rats.
Purpose of the Study:
- To assess the efficacy of IGF-I gene therapy in treating estrogen-induced prolactinomas in a rat model.
- To evaluate the impact of IGF-I gene therapy on prolactin levels and pituitary lactotroph morphology.
Main Methods:
- Estrogen (E2) was used to induce prolactinomas in Sprague Dawley rats.
- Adenoviral vectors carrying rat IGF-I (RAd-IGFI) or green fluorescent protein (RAd-GFP) were injected into the pituitary.
- Serum prolactin (PRL) levels and pituitary lactotroph morphology (cell size and volume density) were analyzed.
Main Results:
- RAd-IGFI administration significantly reduced elevated serum PRL levels compared to the RAd-GFP control.
- IGF-I gene therapy reversed the E2-induced increase in lactotroph cell size.
- The volume density of lactotrophs was also significantly reduced by RAd-IGFI treatment.
Conclusions:
- IGF-I gene therapy is a potentially effective treatment for prolactinomas.
- Bioactive peptide gene delivery represents a novel therapeutic strategy for pituitary tumors.
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