Enhanced delivery of human growth hormone across cell membrane by Tat-PTD

In this study, we utilized the HIV protein Tat protein transduction domain (Tat-PTD) to enhance the intestinal absorption of recombinant human growth hormone (rhGH) delivered by oral administration. Insulin-like growth factor 1 (IGF-1), the key factor in the GH signal transduction pathway, was differentially affected at the mRNA level by various concentrations of rhGH. At high rhGH concentrations (500 ng/ml), IGF-1 was downregulated, while low concentrations (5 ng/ml) caused IGF-1 upregulation. The addition of Tat-PTD had a significant facilitating effect on rhGH. Frozen tissue sections visualized with fluorescence microscopy, cultured cells visualized by confocal microscopy and flow cytometry all confirmed that rhGH fused to Tat-PTD demonstrated more intracellular fluorescent signal when compared to rhGH alone. ELISA showed that after 2 h of incubation, Tat-rhGH levels in the rat intestinal cavity were 1.38-fold higher than rhGH. These data indicated that Tat-PTD effectively improved the internalization of rhGH and enhance the signal transduction of rhGH, possibly laying a solid foundation for the novel oral administration of rhGH.