GHRP-6 vs Sermorelin

GHRP-6

GHRP-6 is a synthetic hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, and one of the earliest growth hormone-releasing peptides to be described. It came out of structure-activity work on small synthetic peptides, carried out before anyone knew which receptor they acted on. That receptor, GHS-R1a, was later shown to respond to ghrelin, a hormone made mainly in the stomach, so GHRP-6 is now classed as a ghrelin receptor agonist. It has been used in pituitary cell and receptor assays, in a large body of animal work, and in human endocrine studies of hormone secretion. Because the same receptor takes part in the control of feeding, it has also served as a tool in appetite research.

Sermorelin

Sermorelin is a synthetic 29-residue peptide reproducing the N-terminal segment of human growth hormone-releasing hormone (GHRH). Native GHRH has 44 residues, and the 1–29 segment, amidated at its C-terminus as here, is reported to retain the receptor activity of the full hormone. Like native GHRH, it is cut quickly by plasma enzymes including dipeptidyl peptidase-4, a property that later analogues such as tesamorelin were modified to avoid. Research on it has centred on growth hormone release from the anterior pituitary, including human physiology studies, many of them decades old, alongside animal and cell work. Recent literature on sermorelin itself is sparse beside that on newer GHRH analogues.

How GHRP-6 acts

GHRP-6 is reported to bind and activate GHS-R1a, a G protein-coupled receptor that signals mainly through Gq, phospholipase C and intracellular calcium. On pituitary somatotrophs this signalling triggers growth hormone release. The receptor is also expressed in the hypothalamus, including on neuropeptide Y and agouti-related peptide neurons of the arcuate nucleus, which rodent studies have linked to the control of food intake; that distribution is the basis for the peptide's use in feeding research. Small increases in ACTH, cortisol and prolactin have been reported with it in addition to growth hormone. Interactions with somatostatin signalling have been proposed but are less clearly defined.

How Sermorelin acts

Sermorelin binds the GHRH receptor, a class B G-protein-coupled receptor on somatotroph cells of the anterior pituitary. Receptor activation has been reported to raise cyclic AMP and activate protein kinase A and the transcription factor CREB, which is linked to transcription of the growth hormone gene as well as to release of stored hormone. Because it acts upstream of the pituitary, the growth hormone released stays subject to inhibition by somatostatin and to negative feedback from IGF-1. This is the main pharmacological difference between GHRH analogues and growth hormone itself.

The records side by side

• Type: GHRP-6, Growth hormone secretagogue (GHRP); Sermorelin, GHRH analog (growth hormone secretagogue)
• Length: GHRP-6, 6 amino acids; Sermorelin, 29 amino acids
• Molecular weight: GHRP-6, 873.0 g/mol; Sermorelin, 3357.9 g/mol
• Molecular formula: GHRP-6, C46H56N12O6; Sermorelin, C149H246N44O42S

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.