Effect of insulin-like growth factor-I gene therapy on the somatotropic axis in experimental prolactinomas.

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-beta 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 microm(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 microm(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. (c) 2008 S. Karger AG, Basel.