title: Systemic action of human growth hormone following adenovirus-mediated gene transfer to rat submandibular glands.
abstract: 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.
authors.affiliation: Gene Therapy and Therapeutics Branch, National Institute of Dental Research, Bethesda, MD 20892, USA.
authors.forename: X
authors.initials: X
authors.lastname: He
authors.forename: C M
authors.initials: CM
authors.lastname: Goldsmith
authors.forename: Y
authors.initials: Y
authors.lastname: Marmary
authors.forename: R B
authors.initials: RB
authors.lastname: Wellner
authors.forename: A F
authors.initials: AF
authors.lastname: Parlow
authors.forename: L K
authors.initials: LK
authors.lastname: Nieman
authors.forename: B J
authors.initials: BJ
authors.lastname: Baum
mesh_terms: 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*
chemical_list: D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone