In a 6‑week study on young dogs, giving hexarelin twice daily first boosted growth‑hormone (GH) spikes, especially at week 3, but the boost faded by week 6. The body’s response to a separate GH‑releasing hormone stayed steady, and the appetite‑stimulating effect of hexarelin disappeared mid‑study then came back later, hinting at different brain receptors.

In this study we evaluated, in six young (5-7 year-old) beagle dogs, the effects of a 6-week administration of hexarelin (250 microg/kg s. c. twice daily) on the GH response to an acute challenge with hexarelin or GHRH (2 microg/kg i.v.), delivered before and after 3 and 6 weeks of treatment. The GH peak response to acute hexarelin or GHRH initially increased, with a maximum observed at the 3rd week, and then decreased to basal values (GHRH) or less (hexarelin) at the 6th week. These data would indicate that hexarelin initially primed the pituitary to acute administration of further hexarelin or of GHRH, followed by downregulation of the GH response to hexarelin and preservation of the response to GHRH. We then studied the rebound increase in GH secretion after withdrawal of an infusion of somatostatin (4 microg/kg per h for 1.5 h), a likely stimulus of endogenous GHRH function. The pattern obtained was similar to, though not superimposable upon, that ensuing after acute hexarelin or GHRH administration. Parallel evaluation of the acute orexigenic effect of hexarelin evinced a different time-course of the behavioural response, namely an acute feeding response to hexarelin that was abolished at the 3rd week and returned to normal at the 6th week. The differing timing of the neuroendocrine or behavioural response to hexarelin would suggest the existence of different subtypes of central nervous system GH-releasing peptide receptors.