Sermorelin, CAS 86168-78-7, is GRF(1-29) amide, the amino terminal twenty nine residues of growth hormone releasing hormone, and it is the shortest fragment of that parent hormone described as retaining full activity at the GHRH receptor in published assays. Ipamorelin, CAS 170851-70-4, has no natural parent. It emerged from a synthetic secretagogue series built around the growth hormone secretagogue receptor and refined for selectivity.
The recorded molecular data make the difference plain. Sermorelin is C149H246N44O42S with an average mass of 3357.93. Ipamorelin is C38H49N9O5 with an average mass of 711.85 and the sequence H-Aib-His-D-2-Nal-D-Phe-Lys-NH2. Sermorelin is close to five times the mass of ipamorelin, and being a natural sequence fragment it is assembled from standard L amino acids, whereas ipamorelin contains aminoisobutyric acid, two D configured residues and a carboxy terminal amide. Those unnatural elements are exactly what give the smaller molecule its protease resistance. A residue sequence for sermorelin is not held in our molecular dataset, so it is described here by fragment identity.
The receptors involved are different proteins with different signaling. The GHRH receptor engaged by sermorelin is a class B G protein coupled receptor that raises cyclic AMP in somatotrophs. The growth hormone secretagogue receptor engaged by ipamorelin is a class A receptor coupled through phospholipase C to intracellular calcium release. In cultured pituitary cell models the two produce distinguishable release kinetics, and each can be blocked selectively by an antagonist of its own receptor, which is the cleanest demonstration that they are not the same tool.
Published pituitary cell work also separates them on selectivity. Sermorelin, as a fragment of the natural hormone, is constrained by the same feedback architecture as the parent, and its effect in cell preparations depends on the somatostatin tone present in the system. Ipamorelin was specifically characterised in rat pituitary cell studies for releasing growth hormone with minimal accompanying release of prolactin, corticotropin or luteinising hormone, a selectivity profile that distinguished it from earlier secretagogues in the same chemical series. Comparing the two therefore requires reporting which pituitary preparation was used, because they respond differently to the same background.
Stability follows size and composition. Sermorelin is a long natural sequence and is susceptible to dipeptidyl peptidase 4 clipping at its amino terminus, a well described liability of GRF fragments, and it contains a methionine, so oxidation is a consideration as well. Ipamorelin, with its amino terminal aminoisobutyric acid, its D residues and its amidated carboxy terminus, is a much harder target for peptidases. Both are supplied lyophilized, stored at minus 20 degrees Celsius protected from light and moisture, reconstituted with gentle swirling, refrigerated at 2 to 8 degrees Celsius in solution, and aliquoted to avoid repeated freeze thaw.
Laboratories pick between them by which receptor the question belongs to, and by how much peptide stability the experiment can tolerate. What remains unsettled is the relationship between acute release measured in cell culture and the pattern seen in intact rodents, where feedback, receptor desensitisation and clearance all reshape the result.