Lung to blood passage of human growth hormone after intratracheal instillation: stimulation of growth in hypophysectomized rats

Abstract

ABSTRACT The passage from the lower respiratory tract into the blood of human GH (hGH; Mr = 22 000) and bovine serum albumin (BSA; Mr = 67 000) was assessed after intratracheal instillation in adult rats. The plasma level of immunoreactive hGH reached its maximum at 0·5–1 h after instillation and had almost disappeared within 24 h. Higher plasma levels were obtained in male rats than in female rats resulting in a higher total lung passage of hGH in male rats than in female rats (means±s.d.; 6·0± 1·7% vs 3·3±1·2%, P <0·01). The plasma level of BSA showed a different pattern, with a maximum at 16–24 h after instillation and a total lung passage of 4·3 ± 1·7% of the given dose for both sexes. The plasma levels of hGH increased non-linearly with increasing dose instilled in the dose range 36–720 μg/kg body weight. When hGH was instilled daily at a dose of 720 μg/kg body weight to hypophysectomized rats for 1 week, they responded with a significant increase in body weight when compared with hypophysectomized control rats (16·8±4·2 g vs −1·8±2·4 g, P <0·001). The results demonstrate that, despite their different molecular weights, hGH and BSA pass through the lower respiratory tract into the circulation with similar efficiencies in the rat. However, the lung passage of hGH, unlike that of BSA, showed sexual dependency, an earlier plasma concentration maximum and a tendency of the passage to saturation with increasing dose instilled. Since hGH was shown to be biologically active after the passage through the lungs, the lung may be a potential new route for hGH administration. Journal of Endocrinology (1992) 134, 197–203