GHRP-6 vs Kisspeptin

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.

Kisspeptin

Kisspeptin-10 is a ten-residue peptide amide, the shortest active member of the kisspeptin family encoded by the KISS1 gene. The gene's 145-residue precursor is processed into kisspeptins of 54, 14, 13 and 10 amino acids, which all share the same C-terminal ten residues ending in Arg-Phe-NH2. Research interest in its reproductive role grew after human genetic studies linked loss of kisspeptin receptor function to a failure to enter puberty. It has since been examined in cell and animal models of hypothalamic reproductive control, and in short human physiological studies that measured gonadotropin release. Longer-term human data are limited.

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 Kisspeptin acts

Kisspeptin-10 has been reported to bind KISS1R, also called GPR54, a G protein-coupled receptor that signals mainly through Gq/11, phospholipase C and intracellular calcium. KISS1R is expressed on gonadotropin-releasing hormone (GnRH) neurons, and kisspeptin signalling is regarded as a principal upstream input controlling their activity. In animal and human physiological studies, exposure has been followed by GnRH release and, downstream, secretion of LH and to a lesser degree FSH from the anterior pituitary. Continuous exposure has been reported in some models to desensitise the receptor, a phenomenon that is itself a topic of study.

The records side by side

• Type: GHRP-6, Growth hormone secretagogue (GHRP); Kisspeptin, Decapeptide (KISS1-derived)
• Length: GHRP-6, 6 amino acids; Kisspeptin, 10 amino acids
• Molecular weight: GHRP-6, 873.0 g/mol; Kisspeptin, 1302.4 g/mol
• Molecular formula: GHRP-6, C46H56N12O6; Kisspeptin, C63H83N17O14

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.