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

CONSOLE GLORIA M,; HEREÑÚ CLAUDIA B; CAMIHORT GISELA A; LUNA GEORGINA C; FERESE CELIA; GOYA RODOLFOG

Cells Tissues and Organs

Karger

Año: 2008

1422-6421

Insulin-like growth factor (IGF-I) provides a physiologic feedback effect within the somatotropic axis. Gene therapy was implemented in young (5 mo.) female Sprague-Dawley rats which received  two pituitary stereotaxic injections of 3 x 109 plaque forming units (pfu) of a control recombinant adenoviral vector (RAd) expressing green fluorescent protein (RAd-GFP) or RAd-IGF-I. The animals were sacrificed 7 days post-injection. Previously, on day –23 the experimental groups received s.c implants of 17-â estradiol. Morphometric analysis revealed that the somatotrope cells in estrogen-treated rats without stereotaxic injections showed a significant (p < .01) increase of the cell size (CS) as compared with intact controls  (59.9 µm2 ± 1.1 vs 42.9 µm2 ± 1.2) and showed a significant (p < .05)  decrease  in cell density (CD) 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 < .05) decrease in  cell size (CS)  with respect to  E2 + Rad-GFP (51.3 µm2 ± 0.3 vs 58.9 µm2 ± 0.3) and no changes in cell density (CD) as compared with RAd-GFP-injected animals (12.8 ± 1.7 vs 10.5 ± 0.1). Serum GH was higher (p < 0.01) in estrogen-treated animals compared with controls (146.7 ng/ml ± 6 vs 73.9 ng/ml ± 9). Injection of RAd-IGF-I in pituitary tumor-bearing rats significantly (p < 0.05) decreased their serum GH levels (107.5 ng/ml ± 7 versus 142.4 ng/ml ± 9, in treated and untreated rats, respectively).  IGF-I gene therapy appears to be an effective approach for the treatement of experimental somatomammotropic pituitary tumors and could be potentially useful as an adjuvant of  conventional therapies.