Overview

Research was conducted to determine if GHRP-6 requires endogenous GHRH presence in order to exert its potential. In one study,⁽⁴⁾ the researchers evaluated the impact of GHRP-6 exposure following either GHRH antagonist or saline presence in the research models. Blood samples were collected incrementally for the next few hours and the concentrations of growth hormones was measured. Following the study, the researchers suggested that hGH levels were lower in models presented with GHRH antagonist. They posited further that endogenous GHRH may be necessary for GHRP-6 to exert potential action.

While the mechanism of GHRP-6 remains under study,⁽⁴⁾ further research studies have suggested that GHRPs may act by binding with two receptors, GHS-R1a, and CD36. In addition to hGH release, GHRP-6 also appears to have the potential to reduce cellular death through binding with CD36 receptors, possibly stimulating prosurvival cellular pathways.⁽²⁾ This remains under investigation.

Earlier it was hypothesized that GHRP-6 may work through a double mechanism, producing possible activities at the pituitary gland and hypothalamus. In a study to investigate this mechanism of action,⁽⁵⁾ two research model groups were evaluated, one group of hypothalamus-pituitary disconnection and one control model. Each subject was either presented GHRH, GHRP-6, or a combination of both. After presentation, the hGH levels were measured in all. In the control group, the highest levels of hGH were found in models given both GHRH and GHRP-6, followed by GHRP-6 models, and lastly the GHRH models. These results appeared to be converse in the research models of hypothalamic pituitary disconnection, with the least levels of HGH reported in those exposed to both GHRP-6 and GHRH. The GHRH subjects appeared to have the same levels of hGH as controls, whereas the hGH levels were reportedly reduced in models exposed to GHRP-6 alone. Two hypotheses were extended by the researchers from this study – first, GHRP-6 action may be induced primarily in the presence of GHRH and second, that GHRP-6 may act on hypothalamic pituitary axis in order to produce its potential.

Furthermore, researchers posited that GHRP-6 may potentially show an affinity toward CD36 receptors. These receptors are thought to fulfill various functions, such as possibly playing a part in lipid metabolism by acting as a scavenger receptor for lipids, aiding in their absorption, and possibly influencing immune responses by controlling phagocytosis and inflammation. The pathways involving CD36 might also have a role in the regulation of angiogenesis.