Comparison of GH‐stimulation by GH‐RH(1‐29)NH₂ and an agmatine²⁹ GH‐RH analog, after intravenous, subcutaneous and intranasal administration and after pulmonary inhalation in rats

Many studies have shown that human GH-RH(1-29)NH₂ possesses full intrinsic activity of GH-RH(1-44)NH₂ in 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 ± 36 ng GH/mL) or for the intranasal group (175 ± 30 ng 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.