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.
Cónsole
Gloria M
GM
Department of Cytology, Histology and Embryology B, CICBA, Faculty of Medicine, National University of La Plata, La Plata, Argentina. gconsole2@gmail.com
Hereñú
Claudia B
CB
Camihort
Gisela A
GA
Luna
Georgina C
GC
Ferese
Celia
C
Goya
Rodolfo G
RG
D000818:Animals; D002452:Cell Count; D048429:Cell Size; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000378:metabolism; D013006:Growth Hormone / Q000097:blood; D020007:Implants, Experimental; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy; D010911:Pituitary Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011388:Prolactin / Q000097:blood; D015175:Prolactinoma / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D052683:Somatotrophs / Q000187:drug effects / Q000473:pathology*
D004967:Estrogens; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D013006:Growth Hormone