GH Secretagogues

In-vitro and preclinical literature on Sermorelin, Ipamorelin and Mod GRF 1-29: mechanisms, model systems and 15 PubMed-linked references.

✔ PubMed-linked citations   ✔ In-vitro and preclinical only   ✔ Research Use Only

Growth hormone secretagogues (GHS) are peptides studied for their interaction with the two receptor systems that regulate somatotroph GH release in preclinical models: the GHRH receptor (GHRH-R, a class B G protein-coupled receptor coupled to adenylate cyclase/cAMP) and the ghrelin receptor GHS-R1a (a class A GPCR coupled to Gq/phospholipase C and calcium signaling). The class is divided into GHRH analogs (GRF 1-29 fragments and their stabilized derivatives) and ghrelin-mimetic growth hormone-releasing peptides (GHRPs) such as ipamorelin. The foundational literature is largely in-vitro pharmacology (rat anterior pituitary membranes and dispersed pituitary cells, receptor cloning and transfected cell lines, plasma-enzyme stability assays) and animal models in rat and swine. Later clinical work exists for several compounds but is outside the scope of this research-use-only library, which focuses on mechanism, structure-activity relationships and model systems.

This page collects 20 peer-reviewed references across 4 compounds. Every citation links to its PubMed record so the primary source can be read in full. The selection is limited to in-vitro, ex-vivo and preclinical animal studies and mechanistic reviews; human clinical literature is deliberately excluded because Liv Pure products are supplied for laboratory research only.

Sermorelin

Also known as: GRF(1-29)-NH2; hGRF(1-29)-NH2; GHRH(1-29) amide; human pancreatic GRF(1-29)

Molecular target or pathway: Pituitary GHRH receptor (GHRH-R), a class B G protein-coupled receptor; activation of adenylate cyclase and cAMP accumulation in somatotrophs

Origin: Synthetic 29-residue N-terminal fragment of endogenous human growth hormone-releasing hormone (GHRH 1-44), C-terminally amidated

Sermorelin is the 1-29 amidated fragment of human GHRH and has been used since the mid-1980s as the reference agonist in GHRH-receptor pharmacology. Rat anterior-pituitary membrane assays established that the 1-29 fragment retains full adenylate cyclase activation and were used to map which residues govern receptor recognition and activation. Plasma-enzymology studies showed rapid dipeptidyl peptidase IV cleavage at the 2-3 bond, which motivated the stabilized analogs elsewhere in this class. Most later sermorelin literature is clinical and is not included here; the references below are limited to receptor, structure-activity and stability work.

Liv Pure supplies Sermorelin as a lyophilized research reagent with a lot-specific certificate of analysis.

Selected references

  1. Robberecht P et al. (1985). Endocrinology. Rat anterior pituitary membrane adenylate cyclase assay. Compared 14 position 1-7 substituted GRF(1-29)-NH2 analogs against the parent peptide for adenylate cyclase activation and identified (N-Ac-Tyr1, D-Arg2)-GRF(1-29)-NH2 as a competitive antagonist, demonstrating that GRF and VIP receptors are distinct in rat pituitary. PMID 2994998 · DOI
  2. Robberecht P et al. (1986). Peptides. Rat adenopituitary, liver and pancreas membranes (adenylate cyclase). Tested 30 synthetic GRF(1-29)-NH2 analogs and reported that the C-terminal region governs GRF-receptor recognition while the N-terminal region is critical for adenylate cyclase activation. PMID 3018703 · DOI
  3. Frohman LA et al. (1989). The Journal of Clinical Investigation. Human plasma enzymology (HPLC) and transgenic pig plasma. Characterized dipeptidyl peptidase IV as the plasma enzyme cleaving GRH(1-29)-NH2 and related fragments at the 2-3 bond, with cleavage blocked by diprotin A or by D-amino acid substitution at position 1 or 2. PMID 2565342 · DOI
  4. Mayo KE et al. (1992). Molecular Endocrinology. Cloned rat/human GHRH receptor expressed in human kidney 293 cells. Reported molecular cloning of a pituitary-specific seven-transmembrane GHRH receptor whose expression in 293 cells conferred high-affinity GHRH binding and cAMP production. PMID 1333056 · DOI
  5. Su CM et al. (1991). Hormone and Metabolic Research. Porcine plasma in vitro stability assay (HPLC). Measured a plasma half-life of approximately 13 minutes for GRF(1-29)-NH2 with GRF(3-29)-NH2 as the primary degradation product. PMID 1826667 · DOI

Ipamorelin

Also known as: NNC 26-0161; Aib-His-D-2-Nal-D-Phe-Lys-NH2; pentapeptide growth hormone-releasing peptide (GHRP class)

Molecular target or pathway: Ghrelin receptor GHS-R1a (growth hormone secretagogue receptor), a class A G protein-coupled receptor; responses in pituitary cells blocked by GHRP-receptor antagonists

Origin: Synthetic pentapeptide derived from the GHRP-1 series by deletion of the central Ala-Trp dipeptide (Novo Nordisk)

Ipamorelin was described in 1998 as a GHRP-receptor agonist that released GH from primary rat pituitary cells with potency similar to GHRP-6 while, unlike GHRP-2 and GHRP-6, not increasing ACTH or cortisol in swine. It became a lead structure for medicinal-chemistry programs on smaller, orally available secretagogues. Later preclinical work has used it as a peripherally restricted ghrelin-receptor agonist in rat gastrointestinal motility and nociception models. Several human studies exist but are outside this library's scope.

Liv Pure supplies Ipamorelin as a lyophilized research reagent with a lot-specific certificate of analysis.

Selected references

  1. Raun K et al. (1998). European Journal of Endocrinology. Primary rat pituitary cells; anesthetized rats; conscious swine. Reported GH release from rat pituitary cells with EC50 of 1.3 nmol/L, blockade by GHRP-receptor but not GHRH antagonists, and no significant change in ACTH, cortisol, FSH, LH, PRL or TSH in swine. PMID 9849822 · DOI
  2. Ankersen M et al. (1998). Journal of Medicinal Chemistry. Rat pituitary cell assay; anesthetized rats; swine and dogs. Described a series of ipamorelin-derived secretagogues with peptidomimetic substitutions and N-methylation and compared their in vitro potency and in vivo GH release to ipamorelin. PMID 9733495 · DOI
  3. Hansen TK et al. (2001). Bioorganic & Medicinal Chemistry Letters. Rat pituitary cell assay; single-dose pig study. Prepared hybrids of NN703 and ipamorelin and reported that re-introducing C-terminal ipamorelin pharmacophores increased in vitro and in vivo potency. PMID 11459660 · DOI
  4. Johansen PB et al. (1999). Growth Hormone & IGF Research. Adult female Sprague-Dawley rats (tetracycline-labelled tibial growth plate). Dose-dependent increases in longitudinal bone growth rate and body weight gain were observed over 15 days without changes in total IGF-I, IGFBPs or serum bone-turnover markers. PMID 10373343 · DOI
  5. Greenwood-Van Meerveld B et al. (2012). Journal of Experimental Pharmacology. Rat postoperative ileus model; isolated gastric fundus organ bath. Intravenous ipamorelin was associated with faster gastric emptying after intestinal manipulation, and 1 uM ipamorelin restored acetylcholine- and field-stimulation-induced contractility in isolated gastric smooth muscle. PMID 27186127 · DOI

Mod GRF 1-29 (CJC-1295 without DAC)

Also known as: Modified GRF(1-29); [D-Ala2, Gln8, Ala15, Leu27]-hGRF(1-29)-NH2; tetrasubstituted GRF(1-29); CJC-1295 no DAC

Molecular target or pathway: Pituitary GHRH receptor (GHRH-R); adenylate cyclase/cAMP signaling in somatotrophs; designed for resistance to dipeptidyl peptidase IV and trypsin-like plasma cleavage

Origin: Synthetic analog of the GRF(1-29) fragment of human GHRH carrying four amino-acid substitutions; identical to the peptide backbone of CJC-1295 without the C-terminal maleimidopropionyl-lysine (DAC) group

Mod GRF 1-29 is the tetrasubstituted hGRF(1-29) backbone from which CJC-1295 was built. Its substitutions come directly from 1980s-1990s structure-activity work on rat pituitary systems: D-Ala2 blocks dipeptidyl peptidase IV cleavage at the 2-3 bond and behaved as a super-agonist in rat pituitary adenylate cyclase assays, Ala15 increased potency in the rat pituitary bioassay, and Gln8/Leu27 replace oxidation- and deamidation-prone residues. The analog itself has little dedicated primary literature; the references below cover the component substitutions and the DPP-IV stability data that define it.

Liv Pure supplies Mod GRF 1-29 (CJC-1295 without DAC) as a lyophilized research reagent with a lot-specific certificate of analysis.

Selected references

  1. Robberecht P et al. (1985). Endocrinology. Rat anterior pituitary membrane adenylate cyclase assay. Among D-amino acid substitutions in positions 1-7 of GRF(1-29)-NH2, only the D-isomer at position 2 yielded a super-agonist, with a Kact two-fold lower than the parent peptide. PMID 2994998 · DOI
  2. Su CM et al. (1991). Hormone and Metabolic Research. Porcine plasma in vitro stability assay (HPLC). Ala15 substitution modestly prolonged GRF(1-29)-NH2 plasma half-life, and a D-amino acid at position 2 or absence of a free N-terminal amine completely prevented cleavage between positions 2 and 3. PMID 1826667 · DOI
  3. Frohman LA et al. (1989). The Journal of Clinical Investigation. Human plasma enzymology (HPLC). Identified dipeptidyl peptidase IV and trypsin-like enzymes as the primary plasma degradation routes for GRH(1-29)-NH2 and confirmed that analogs designed to resist these enzymes showed enhanced plasma stability. PMID 2565342 · DOI
  4. Bongers J et al. (1992). Peptide Research. Enzymatic semisynthesis; rat pituitary bioassay and receptor binding. [Ala15]-GRF(1-29)-NH2 prepared by alpha-amidating enzyme catalysis showed full potency in an in vitro rat pituitary bioassay and full receptor-binding affinity, and was described as a superactive analog relative to GRF(1-29)-NH2. PMID 1421807
  5. Jette L et al. (2005). Endocrinology. Cultured rat anterior pituitary cells; Sprague-Dawley rats. Tetrasubstituted hGRF(1-29) maleimido derivatives showed enhanced in vitro stability against dipeptidyl peptidase IV and retained GH-secretion activity in cultured rat anterior pituitary cells. PMID 15817669 · DOI

Frequently asked questions

What are the molecular targets used to distinguish the two sub-groups of this class in the literature?

GHRH-derived peptides (sermorelin, Mod GRF 1-29, CJC-1295) are characterized against the pituitary GHRH receptor, a class B GPCR that increases cAMP through adenylate cyclase (Mayo 1992; Robberecht 1985). Ghrelin-mimetic peptides such as ipamorelin are characterized against GHS-R1a, the receptor cloned by Howard et al. (1996), and their responses in pituitary-cell assays are blocked by GHRP-receptor antagonists rather than GHRH antagonists (Raun 1998). Studies combining the two ligand types in rat systems report greater-than-additive GH release (Bowers 1991).

Which model systems appear most often in the primary literature for these compounds?

Rat anterior-pituitary membrane adenylate cyclase assays and dispersed primary rat pituitary cell GH-release assays are the standard in-vitro systems; transfected HEK293-type cells expressing cloned GHRH-R or GHS-R1a are used for binding and second-messenger work. In vivo characterization has used pentobarbital-anesthetized rats and conscious swine for plasma GH measurements. Plasma stability is typically assessed by incubating the peptide in rat, porcine or human plasma at 37 C and following degradation products by HPLC or LC-MS/MS.

What handling considerations follow from the published stability data?

The literature shows that unmodified GRF(1-29)-NH2 is cleaved rapidly at the Ala2-Ala3 bond by dipeptidyl peptidase IV in plasma (half-life on the order of minutes in porcine plasma), and that D-Ala2 substitution or N-terminal modification prevents this cleavage (Frohman 1989; Su 1991). For bench work this means lyophilized peptides should be reconstituted in an appropriate sterile, DPP-IV-free buffer immediately before assay, kept cold, and protected from repeated freeze-thaw; CJC-1295 additionally carries a reactive maleimide that will covalently bind free thiols, including albumin or cysteine-containing additives, in the assay medium (Jette 2005). The literature does not cover shelf-life of reconstituted solutions under typical lab storage, so users should establish this empirically.

All compounds referenced on this page are supplied by Liv Pure for in-vitro laboratory research only and are not for human or animal use. Nothing on this page is medical advice, and no statement here has been evaluated by the Food and Drug Administration. Product identity and purity for each lot are documented on the certificate of analysis; our Testing and Quality page explains what those certificates do and do not measure. Browse the GH Secretagogues category to see current lots.

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