Sermorelin is the laboratory name for GHRH(1-29)NH2, an amidated 29-amino-acid peptide corresponding to the biologically active N-terminal fragment of growth-hormone-releasing hormone (GHRH). Native human GHRH is a 44-amino-acid peptide produced in the hypothalamus, but pharmacology work going back decades established that the first 29 residues, capped with a C-terminal amide, retain essentially the full receptor-binding and signaling activity of the intact molecule in pituitary cell and tissue models. Researchers use sermorelin as a defined, stable tool for studying growth-hormone-releasing hormone receptor (GHRHR) signaling in somatotroph cells without needing the full-length native peptide.
| Attribute | Detail |
|---|---|
| Name | Sermorelin, also written GHRH(1-29)NH2 or GRF(1-29)NH2 |
| Class | Amidated 29-amino-acid peptide fragment of growth-hormone-releasing hormone |
| Sequence length | 29 amino acids, C-terminal amide |
| Origin | N-terminal fragment of the 44-amino-acid native GHRH molecule |
| Receptor target | Growth-hormone-releasing hormone receptor (GHRHR), a G-protein-coupled receptor on pituitary somatotrophs |
| What studies examine | cAMP accumulation and GH release in pituitary cell culture, GHRHR structure-function, rodent and genetic models of GHRHR loss of function |
| Form supplied | Lyophilized powder, research use only |
What is the structure of sermorelin?
Native GHRH is a 44-amino-acid peptide, but researchers characterizing its structure-activity relationship found that the first 29 residues, synthesized with a C-terminal amide group in place of the free acid, reproduce the receptor-binding and GH-releasing activity of the full peptide in pituitary tissue and cell assays. This 29-residue amidated fragment is what laboratories refer to as sermorelin, GRF(1-29)NH2, or GHRH(1-29)NH2 interchangeably in the literature. Lefrançois and Gaudreau (1994) mapped the pharmacophore regions within this sequence using binding assays in rat adenopituitary tissue, work that helped define which residues in the fragment are required for receptor engagement.
What receptor does sermorelin act on, and how was it identified?
Sermorelin's target is the growth-hormone-releasing hormone receptor, a G-protein-coupled receptor expressed on pituitary somatotroph cells. Mayo (1992) reported the molecular cloning and expression of this pituitary-specific receptor, establishing it as a distinct member of the class B GPCR family coupled to Gs and adenylate cyclase. Mayo's later review (2000) summarized how GHRH binding to this receptor activates cAMP production, which in turn drives both GH gene transcription and acute GH secretion from somatotroph cells, the two processes researchers track when studying GHRH-axis compounds in pituitary cell culture.
What have pituitary cell culture studies examined?
Cell-based work on the GHRH sequence and its receptor spans several decades of endocrine pharmacology. Cheng et al. (1989) studied the interaction between a GH-releasing hexapeptide and GHRH-family peptides in rat primary pituitary cell culture, measuring both GH release and intracellular cAMP accumulation and reporting a synergistic effect between the two classes of secretagogue acting through separate receptors. Cunha and Mayo (2002) examined how ghrelin and other GH secretagogues affect GHRH-induced cAMP production in cells engineered to express both the GHRH receptor and the GH secretagogue receptor, mapping how the two signaling pathways interact at the cellular level. Rekasi and Schally (1993) developed a superfusion bioassay system in rat pituitary tissue specifically to evaluate the activity of GHRH analogs, a method that became a standard tool for comparing GHRH-fragment potency in later structure-activity work.
What have genetic and animal models examined?
Naturally occurring loss-of-function mutations in the GHRH receptor gene provided an early animal model for understanding GHRH-axis biology. The "little" (lit) mouse carries a missense mutation in the GHRH receptor that disrupts receptor function and produces a dwarf phenotype with low circulating GH. Wajnrajch et al. (1996) reported a nonsense mutation in the human GHRH receptor gene that produces a growth-failure phenotype described as analogous to the little mouse, linking the rodent genetic model directly to human receptor biology and giving researchers a comparative framework for studying GHRHR loss of function across species. Because both the mouse mutation and the human mutation disrupt the same receptor at the molecular level, researchers have used the lit mouse as a genetic tool for testing candidate GHRH-axis compounds and receptor constructs in a background where endogenous receptor signaling is already absent, which helps isolate the specific contribution of an introduced ligand or receptor variant from the animal's baseline physiology.
How do researchers distinguish sermorelin's receptor pharmacology from other secretagogues in an assay?
A recurring methodological question in this literature is how to tell whether a given compound is acting through the GHRH receptor rather than through the separate GH secretagogue receptor that ghrelin-mimetic compounds engage. Cell lines engineered to express only one receptor or the other, as used by Cunha and Mayo (2002), let researchers isolate cAMP signaling specific to each pathway and then look at what happens when both receptor types are present together. Rat pituitary cell culture and the superfusion bioassay approach Rekasi and Schally (1993) developed serve a related purpose, allowing direct comparison of GHRH-fragment potency against reference compounds within the same tissue preparation rather than across separate experiments.
How does sermorelin relate to other GHRH-axis research peptides?
Sermorelin, TH9507 and the ghrelin-receptor-targeting secretagogues such as ipamorelin all intersect with the growth-hormone axis but act through different mechanisms and different molecular starting points. Sermorelin is the minimal active fragment of native GHRH itself, while TH9507 is a chemically stabilized GHRH analog engineered to resist enzymatic breakdown, a distinction covered in more detail in what is TH9507. Ipamorelin and other ghrelin-mimetic secretagogues act on a separate receptor entirely, the GH secretagogue receptor, rather than the GHRH receptor; see what is ipamorelin for that comparison. A broader side-by-side of how these compounds fit together in the published literature is in growth hormone secretagogues in research.
Frequently asked questions
Is sermorelin the same molecule as native GHRH?
No. Native GHRH is a 44-amino-acid peptide; sermorelin is the amidated 29-residue N-terminal fragment that structure-activity studies identified as sufficient to reproduce GHRH receptor binding and signaling in pituitary cell and tissue assays.
What receptor does sermorelin engage?
The growth-hormone-releasing hormone receptor (GHRHR), a class B G-protein-coupled receptor on pituitary somatotroph cells that couples to Gs and adenylate cyclase, first cloned and characterized by Mayo (1992).
How is the little (lit) mouse relevant to sermorelin research?
The lit mouse carries a naturally occurring GHRH receptor mutation that disrupts receptor signaling, producing a well-characterized animal model of GHRH-axis loss of function. Wajnrajch et al. (1996) reported an analogous human receptor mutation, connecting the two as comparative models for receptor biology.
How does sermorelin differ from GHRP-family secretagogues studied alongside it?
Sermorelin acts on the GHRH receptor, while GHRP-family peptides and ghrelin-mimetic secretagogues act on a separate receptor, the GH secretagogue receptor. Cunha and Mayo (2002) and Cheng et al. (1989) both examined how these two pathways interact when studied together in cell and tissue assays.
How is sermorelin supplied for laboratory use?
As a lyophilized powder intended for research use only, sold by lot with an accompanying certificate of analysis, consistent with how other short research peptides on this site are supplied. See our sermorelin lot page for current specifications.
References
- Mayo KE. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol Endocrinol. 1992;6(10):1734-1744. PubMed 1333056.
- Mayo KE, Miller T, DeAlmeida V, et al. Regulation of the pituitary somatotroph cell by GHRH and its receptor. Recent Prog Horm Res. 2000;55:237-266. PubMed 11036940.
- Wajnrajch MP, Gertner JM, Harbison MD, et al. Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse. Nat Genet. 1996;12(1):88-90. PubMed 8528260.
- Rekasi Z, Schally AV. A method for evaluation of activity of antagonistic analogs of growth hormone-releasing hormone in a superfusion system. Proc Natl Acad Sci U S A. 1993;90(6):2146-2149. PubMed 8460121.
- Cunha SR, Mayo KE. Ghrelin and growth hormone (GH) secretagogues potentiate GH-releasing hormone (GHRH)-induced cyclic adenosine 3',5'-monophosphate production in cells expressing transfected GHRH and GH secretagogue receptors. Endocrinology. 2002;143(12):4570-4582. PubMed 12446584.
- Cheng K, Chan WW, Barreto A Jr, et al. The synergistic effects of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 on growth hormone (GH)-releasing factor-stimulated GH release and intracellular adenosine 3',5'-monophosphate accumulation in rat primary pituitary cell culture. Endocrinology. 1989;124(6):2791-2798. PubMed 2541999.
- Lefrançois L, Gaudreau P. Identification of receptor-binding pharmacophores of growth-hormone-releasing factor in rat adenopituitary. Neuroendocrinology. 1994;59(4):363-370. PubMed 8202217.
Research use only. Homegrown Peptides products are for laboratory research and are not for human or animal use. Nothing in this article is medical advice.
