Many studies have shown that human GH‐RH(1‐29)NH2 possesses full intrinsic activity of GH‐RH(1‐44)NH2in vitro and in vivo. This investigation was performed to evaluate the efficacy of GH‐RH(1‐29)NH2 given by different routes of administration in stimulating GH release in rats. In each case GH‐RH(1‐29)NH2 was administered intravenously, subcutaneously, intranasally and by pulmonary inhalation at two different doses to groups of seven male rats. At a dose of 150 μg/kg GH‐RH(1‐29)NH2, the magnitude of GH response was significantly higher for the pulmonary inhalation group (355 ± 33.2 ng GH/mL) than for the subcutaneous group (246 ± 36ng GH/mL) or for the intranasal group (175 ± 30ng GH/mL). The group injected intravenously with GH‐RH(1‐29)NH2 at a dose of 2.5 μg/kg showed the highest response, GH levels reaching 877.2 ± 115 ng/mL. A similar pattern of responses was obtained for the superactive GH‐RH(1‐29) agmatine29 analog, MZ–3‐149, at doses that were 50 times lower. Our results indicate a high bioavailability of GH‐RH(1‐29)NH2 or analog MZ‐3‐149 administered by a convenient pulmonary inhalation route. The GH‐releasing effect of GH‐RH(1‐29)NH2 or analog MZ‐3‐149 delivered by pulmonary inhalation is superior to subcutaneous and intranasal administration.
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