Systemic action of human growth hormone following adenovirus-mediated gene transfer to rat submandibular glands

被引:79
作者
He, X
Goldsmith, CM
Marmary, Y
Wellner, RB
Parlow, AF
Nieman, LK
Baum, BJ
机构
[1] NIDR, GTTB, NIH, Bethesda, MD 20892 USA
[2] NICHD, Dev Endocrinol Branch, Bethesda, MD USA
[3] Univ Calif Los Angeles, Harbor Gen Hosp, Pituitary Hormones & Antisera Ctr, Torrance, CA USA
关键词
gene therapeutics; systemic protein delivery; growth hormone; salivary glands;
D O I
10.1038/sj.gt.3300622
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:537 / 541
页数:5
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