SYSTEMIC ACTION OF HUMAN GROWTH-HORMONE FOLLOWING ADENOVIRUS-MEDIATEDGENE-TRANSFER TO RAT SUBMANDIBULAR GLANDS

We have previously suggested that although salivary glands function in an exocrine manner they might none the less offer a useful way to del iver therapeutic proteins systemically. As a direct functional test of this hypothesis, we constructed a recombinant adenovirus (AdCMVhGH) e ncoding human growth hormone (hGH) and then studied the biological act ion of hGH produced following transfer of the hGH gene to rat submandi bular glands. At 48 h following infusion of AdCMVhGH into these glands via cannulation of the main excretory duct, serum levels of hGH were approximately 16 ng/ml and rat insulin-like growth factor-1 was elevat ed approximately 25%. Moreover, serum chemistry profiles of rats subje cted to in vivo gene transfer displayed alterations in the BUN:creatin ine ratio and triglyceride levels presumably reflecting the anabolic a ctions of the hGH. These results provide the first demonstration of sy stemic biological action from a transgene product secreted in an endoc rine fashion from the salivary glands.