The effects of a continuous infusion of hexarelin on pulsatile growth hormone release, growth axis and galanin gene expression and on the response of the growth axis to growth hormone-releasing hormone

Abstract

The effect of a 6 hour continuous infusion of Hexarelin (100 micrograms/hour) on GH peak frequency, amplitude and duration, GH trough concentrations, the interval between successive peaks and the pituitary responsiveness to GHRH, as well as GH axis and galanin mRNA contents, were examined in conscious adult male rats. Plasma GH concentrations peaked within 15 minutes after the initiation of Hexarelin infusion, but returned to baseline levels by 60 minutes. No significant differences between Hexarelin and saline infused rats were noted for any of the parameters of pulsatile GH release analyzed. However, following a 6 hour infusion, rats treated with Hexarelin demonstrated a greater GH responsiveness to GHRH (delta GH: 57 +/- 16 ng/ml for Hexarelin infused; 21 +/- 7 ng/ml for saline infused; p < 0.05). Furthermore, the rats infused with Hexarelin demonstrated decreased GHRH and increased hypothalamic galanin mRNA contents as compared to the saline infused rats, while hypothalamic somatostatin and pituitary GH mRNA contents appeared unchanged. Rats infused with Hexarelin had lower pituitary galanin mRNA content than did the rats which were infused with saline. Collectively, these results suggest that Hexarelin may not act via alteration of somatostatin synthesis and that suppression of somatostatin's action at the pituitary can not be excluded. The current study also suggests that other hypothalamic pathways aside from those currently defined for the growth axis may be involved in the mechanism by which Hexarelin and the other GH-releasing peptides elicit GH release.