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

Abstract

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.

Site-Specific PEGylation for High-Yield Preparation of Lys21-Amine PEGylated Growth Hormone-Releasing Factor (GRF) (1−29) using a GRF(1−29) Derivative FMOC-Protected at Tyr1 and Lys12

“…Growth hormone-releasing factor (GRF) is attracting growing interest because it acts as an alternative treatment to growth hormone (GH) (1). GRF has two beneficial therapeutic issues vs GH: first, it induces physiological GH-release mimicking the natural pattern; and second, it can be administered via nonparenteral routes (2)(3) due to its small molecular size. Upon release into the circulation, however, GRF , the shortest and fully active form of GRF, is rapidly inactivated by proteolysis of dipeptidyl peptidase IV (DPP IV) (4) and glomerular filtration, with a short plasma half-life of 10-20 min (5).…”