Systemic action of human growth hormone following adenovirus-mediated gene 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 deliver therapeutic proteins systemically. As a direct functional test of this hypothesis, we constructed a recombinant adenovirus (AdCMVhGH) encoding human growth hormone (hGH) and then studied the biological action of hGH produced following transfer of the hGH gene to rat submandibular 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 elevated approximately 25%. Moreover, serum chemistry profiles of rats subjected to in vivo gene transfer displayed alterations in the BUN:creatinine ratio and triglyceride levels presumably reflecting the anabolic actions of the hGH. These results provide the first demonstration of systemic biological action from a transgene product secreted in an endocrine fashion from the salivary glands.
He
X
X
Gene Therapy and Therapeutics Branch, National Institute of Dental Research, Bethesda, MD 20892, USA.
Goldsmith
C M
CM
Marmary
Y
Y
Wellner
R B
RB
Parlow
A F
AF
Nieman
L K
LK
Baum
B J
BJ
D000256:Adenoviridae; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D015870:Gene Expression; D018014:Gene Transfer Techniques; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013363:Submandibular Gland / Q000378:metabolism*
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone