Sermorelin, GHRP-6, GHRP-2 and hexarelin: two doors, four clocks

Sermorelin is growth-hormone-releasing hormone chopped to its first twenty-nine amino acids. That stretch is enough to wake the GHRH receptor on the somatotroph: Gs raises cAMP, and the cell releases a pulse of growth hormone. The native fragment is destroyed in minutes, which is why the stimulation test that used it was a brief pulse and not a weekend. The catalogue molecule people compare it with, CJC without DAC, is the same twenty-nine with four substitutions so the enzymes take longer. Tesamorelin is the forty-four-residue licensed analogue with a different cap. Three peptides, one receptor, three clocks. Sermorelin is the shortest clock and the oldest name. It is not a ghrelin drug. If a vial is raising hunger and cortisol, it is not behaving like sermorelin.

In short. Sermorelin is the first 29 amino acids of GHRH. It pulses growth hormone and is gone in minutes. CJC without DAC is that peptide reinforced. It is not a ghrelin drug, so hunger is not its signature.

The other door is the ghrelin receptor, GHSR. GHRP-6 is the hexapeptide Bowers built, and it is an honest ghrelin mimic. GHSR is Gq-coupled, so calcium rises in the somatotroph and growth hormone leaves, and with GHRP-6 cortisol and prolactin leave too. That rise showed up in the first human tables. GHRP-2 is the successor, still potent at the receptor, a little less comic about appetite in some comparisons, and still not clean on the ACTH line. Hexarelin is the strongest GH releaser of the three and the one that desensitises fastest if you occupy the receptor without a break. It also has a small cardiac literature of its own, separate from the growth hormone it releases, which is a reason not to file it as 'GHRP-6 but more'. Ipamorelin, Raun 1998, is the pentapeptide that finally split GH release from the cortisol and prolactin release. That split is the whole reason ipamorelin has a page of its own and these three share one.

In short. GHRP-6, GHRP-2 and hexarelin hit the ghrelin receptor. They release growth hormone and also cortisol and prolactin. Hexarelin is the strongest and fades fastest. Ipamorelin was made to skip the cortisol and prolactin.

Bowers showed that a GHRH analogue plus a ghrelin mimetic releases more growth hormone than the sum of either alone. The cell is using two second messengers. GHRH works through Gs and cAMP. Ghrelin works through Gq. Somatostatin is still the off-switch, and it can close both conversations. A pulse is large when both doors are knocked and the off-switch is not. A pulse is small when you only tickle one door, or when glucose and somatostatin have the cell in a sulk. This is why the stack of a short GHRH peptide with a short ghrelin peptide became a habit, and why it is not the same object as MK-677. MK-677 sits in the ghrelin receptor for a day. It does not hand the trough back. Sermorelin and GHRP-6, if they are actually those peptides, are gone in well under an hour. The information in a GH pattern lives in the gaps. Filling the gaps is a different drug, even when the receptor name matches.

In short. Knocking both doors at once releases more growth hormone than either door alone. The gap before the next knock is part of the signal. An all-day ghrelin drug like MK-677 never gives the gap back.

Desensitisation is the part the forums skip because the first week feels like the pharmacology. GHSR internalises. A hexarelin schedule that occupies it continuously gets a smaller GH answer as the days go on. Sermorelin's GHRH receptor has its own brake, and a constant GHRH tone, which is what CJC with DAC produced in the Teichman study, raises IGF-1 by abandoning the pulse. You can choose a pulse or you can choose a plateau. Calling both of them 'GH peptides' is how the plateau gets blamed on the pulse, and the other way round. Identity of the chain, which door, how long it sits: three questions. The answers are already in the papers. Hunger means the ghrelin door. No hunger and a brief GH rise means you are probably on the GHRH door, or on ipamorelin. Cortisol and prolactin rising beside the GH means you are not on ipamorelin.

In short. Hit the ghrelin receptor constantly and the response fades. A short pulse and an all-day signal are different drugs. Hunger, cortisol and prolactin tell you which door you actually opened.