GHRP-6

GHRP-6 existed long before ghrelin was known: the hexapeptide described in 1984 released growth hormone dose-dependently in cell cultures and several animal species without dragging prolactin, TSH, LH or FSH along. Asking what it binds to led in 1996 to the cloning of a G protein-coupled receptor found in hypothalamus and pituitary, and in 1999 to the discovery of ghrelin as that receptor's natural ligand: a stomach peptide of 28 amino acids carrying an octanoyl group on serine 3.

Further findings:

• Given centrally, ghrelin and GHRP-6 made rats eat more and switched on the appetite centres of hypothalamus and brainstem; blocking the NPY Y1 receptor abolished the effect (2002).
• A 2017 review collects the cell-protective effects that GHRPs show in preclinical models, carried by GHS-R1a and CD36, for instance in cells of heart, nerve, gut and liver.
• Animal models document both clear GH rises and altered feeding behaviour.

Mechanistically GHRP-6 is an agonist at GHS-R1a on somatotroph cells and triggers pulsatile GH release there, just like GHRP-2. What separates it from GHRP-2 and even more from selective ipamorelin is the hunger component: no other family member reproduces the profile of the "hunger hormone" ghrelin so plainly. For questions around the ghrelin-appetite pathway that is an asset; for clean GH measurements it is a confounder. The half-life is roughly 15 to 30 minutes, and the compound's history reaches back into the 1980s, when GHRP-6 contributed substantially to understanding the ghrelin axis.

Observed in studies and user reports:

• Markedly increased appetite, stronger with GHRP-6 than with any other GHRP.
• Local reactions at the injection site such as redness, pressure or brief irritation.
• Transient fluid retention, tingling or numbness in the hands, described in the literature as dose-dependent and reversible.
• Moderately raised cortisol and prolactin, as with all non-selective members of the class.
• Long-term human data are missing; the picture rests on short studies and anecdotal experience.

This summary is no substitute for medical advice.

• On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone - first description from 1984.
• A receptor in pituitary and hypothalamus that functions in growth hormone release - cloning of the target receptor.
• Ghrelin is a growth-hormone-releasing acylated peptide from stomach - discovery of the natural ligand.