Chronic in vivo Ipamorelin treatment stimulates body weight gain and growth hormone (GH) release in vitro in young female rats

The pentapeptide Ipamorelin stimulates growth hormone (GH) release in pigs, sheep, dogs, rats and humans. In order to determine the effects of chronic treatment with Ipamorelin on the in vitro GH response, Ipamorelin was administered daily for 21 days to 60-day old female rats and the effects compared with those of growth hormone-releasing hormone (GHRH) (10 μg/kg body weight). Daily monitoring revealed a higher % weight gain in the Ipamorelin-pretreated group (IPG) and the GHRH-pretreated group (GPG) than in the vehicle-pretreated group (VPG). In 3-day pituitary cell monolayer cultures, basal GH release was greater in IPG and GPG than in VPG. After 3-day culture, basal GH release from individual cells was lower in IPG than in VPG and GPG. The intracellular GH content was lower in IPG and GPG than in VPG (P<0.05). In 3-day monolayer cultures, Ipamorelin (10-8 M) and GHRH (10-8 M) increased GH release in VPG and IPG, but not in GPG. Similarly, Ipamorelin (10-8 M) and GHRH (10-8 M) stimulated individual GH release in VPG and IPG. In conclusion, these data show that chronic administration of Ipamorelin to young female rats is effective in increasing body weight gain and enhancing in vitr o basal and Ipamorelin or GHRH-stimulated GH release. In the same conditions, GHRH increases body weight gain and maintains basal GH at levels similar to those produced by Ipamorelin, but without prompting any in vitro enhancement of the GH response to subsequent stimuli. These results suggest that Ipamorelin does not lead to desensitization of the GH response in young female rats, whilst GHRH produces desensitization of GH release in vitro.