Effect of Insulin-Like Growth Factor-I Gene Therapy on the Somatotropic Axis in Experimental Prolactinomas

• Published in: Cells, tissues, organs Vol. 190; no. 1; pp. 20 - 26
• Main Authors: Cónsole, Gloria M., Hereñú, Claudia B., Camihort, Gisela A., Luna, Georgina C., Ferese, Celia, Goya, Rodolfo G.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2009
• Subjects: Animals; Cell Count; Cell Size; Estrogens - administration & dosage; Estrogens - pharmacology; Female; Genetic Therapy; Green Fluorescent Proteins - metabolism; Growth Hormone - blood; Implants, Experimental; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - therapeutic use; Neoplasms, Experimental - blood; Neoplasms, Experimental - genetics; Neoplasms, Experimental - pathology; Neoplasms, Experimental - therapy; Original Paper; Pituitary Neoplasms - blood; Pituitary Neoplasms - genetics; Pituitary Neoplasms - pathology; Pituitary Neoplasms - therapy; Prolactin - blood; Prolactinoma - blood; Prolactinoma - genetics; Prolactinoma - pathology; Prolactinoma - therapy; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Somatotrophs - drug effects; Somatotrophs - pathology; Insulin-like growth factor-I; Rat; Somatotropic axis; Gene therapy; Estrogen; Prolactinomas
• ISSN: 1422-6405; 1422-6421
• DOI: 10.1159/000166609

Insulin-like growth factor-I (IGF-I) provides a physiologic feedback effect within the somatotropic axis. Gene therapy was implemented in young female Sprague-Dawley rats which received 2 pituitary stereotaxic injections of a control recombinant adenoviral vector expressing green fluorescent protein (RAd-GFP) or IGF-I (RAd-IGF-I). The animals were sacrificed 7 days after injection. Previously, on day –23, the experimental groups received subcutaneous implants of 17-β estradiol. Morphometric analysis revealed that the somatotrope cells in estrogen-treated rats without stereotaxic injections showed a significant (p < 0.01) increase in the cell size compared with intact controls (59.9 ± 1.1 vs. 42.9 ± 1.2 μm 2 ) and had a significant (p < 0.05) decrease in cell density with respect to intact animals (10.5 ± 0.1 vs. 19.7 ± 1.7). The treatment of pituitary adenomas with RAd-IGF-I induced a significant (p < 0.05) decrease in cell size with respect to E 2 + RAd-GFP (51.3 ± 0.3 vs. 58.9 ± 0.3 μm 2 ) and no changes in cell density compared with RAd-GFP-injected animals (12.8 ± 1.7 vs. 10.5 ± 0.1). Serum growth hormone was higher (p < 0.01) in estrogen-treated animals versus controls (146.7 ± 6 vs. 73.9 ± 9 ng/ml). In rats carrying estrogen-induced adenomas, RAd-IGF-I injection induced a significant (p < 0.05) decrease in serum growth hormone compared to RAd-GFP-injected animals (107.5 ± 7 vs. 142.4 ± 9 ng/ml). IGF-I gene therapy appears to be an effective approach for the treatment of experimental somatomammotropic pituitary tumors and could be potentially useful as an adjuvant of conventional therapies.