Growth hormone secretagogues are synthetic peptides that act on the pituitary and hypothalamus to increase endogenous growth hormone (GH) release rather than supplying GH itself. They fall into two pharmacologically distinct families: GHRH analogues (sermorelin, tesamorelin, CJC-1295) that bind the GHRH receptor, and growth hormone-releasing peptides or GHRPs (ipamorelin, GHRP-2, GHRP-6, hexarelin) that bind the ghrelin receptor GHS-R1a. This guide is written for laboratory researchers comparing the two families in vitro and in preclinical models.
Key takeaways
- Two receptor families, one output. GHRH analogues signal through the GHRH receptor (Gs/cAMP); GHRPs signal through GHS-R1a (Gq/IP3–Ca2+). Both converge on somatotroph GH release.
- GHRPs are synthetic ghrelin mimetics. The receptor was cloned in 1996 by Howard and colleagues before its natural ligand ghrelin was identified by Kojima and colleagues in 1999.
- Ipamorelin was described by Raun and colleagues in 1998 as the first GHRP with a selectivity profile that separated GH release from adrenocorticotropic hormone and prolactin release in preclinical models.
- CJC-1295 exists in two distinct forms: with a drug affinity complex (DAC) that binds serum albumin, and without DAC — the latter is the tetrasubstituted GRF(1-29) analogue commonly listed as Modified GRF 1-29.
- Teichman and colleagues (JCEM, 2006) reported prolonged GH and IGF-I elevation after single administration of CJC-1295 with DAC; Ionescu and Frohman (JCEM, 2006) reported that GH pulsatility persisted under continuous GHRH-receptor stimulation.
- Molecular weights differ by more than an order of magnitude across the class — from 711.9 Da (ipamorelin) to 5135.9 Da (tesamorelin) — which changes the molar concentration of any given mg/mL stock solution.
- All compounds described here are supplied by GenoPept as lyophilised vials for laboratory research only, with a per-batch certificate of analysis.
What are growth hormone secretagogues?
Growth hormone secretagogues (GHS) are compounds that stimulate the pituitary to release its own stored growth hormone, in contrast to recombinant somatropin, which is the 191-amino-acid hormone itself. The research literature divides them into two peptide families defined by which receptor they occupy: the GHRH receptor or the growth hormone secretagogue receptor 1a (GHS-R1a, the ghrelin receptor).
That distinction matters more than any marketing category. A GHRH analogue is a modified fragment of the endogenous 44-residue releasing hormone and can only amplify a signal the hypothalamus already sends. A GHRP is a small, largely unnatural peptide built around D-amino acids that mimics ghrelin, a gut-derived hormone with no structural relationship to GHRH at all.
Because the two families use separate G-protein pathways, they are frequently studied in combination in the published literature — the classic demonstration that a GHRH analogue and a GHRP together produce a larger somatotroph response than either alone.
How the GH axis is regulated
GH secretion is pulsatile, set by the interplay of two hypothalamic peptides: GHRH drives release, somatostatin restrains it, and the alternation between them generates discrete bursts rather than a steady output. Steyn and colleagues review this dual-control model in detail in Comprehensive Physiology.
Ghrelin adds a third input. Discovered in 1999 as the endogenous ligand for the orphan receptor cloned three years earlier, it is an octanoylated 28-residue peptide from the stomach that acts at GHS-R1a in both the pituitary and the arcuate nucleus.
Downstream, GH acts on hepatocytes to induce IGF-I, and circulating IGF-I feeds back negatively on the hypothalamus and pituitary. Any experimental design using a secretagogue is therefore working inside a closed loop — the reason investigators typically sample GH over a time course rather than at a single point.
Family 1: GHRH analogues
GHRH analogues are truncated and stabilised versions of human growth hormone-releasing hormone, a 44-residue hypothalamic peptide. The 1-29 fragment retains essentially full receptor activity, making it the scaffold from which sermorelin, Modified GRF 1-29 and CJC-1295 are all built.
Sermorelin (GRF 1-29)
Sermorelin is the unmodified 29-residue fragment, CAS 86168-78-7, C149H246N44O42S, MW 3357.9 Da. It is the reference GHRH-receptor agonist in this class and has been used historically as a diagnostic probe of pituitary GH reserve. Its brevity in circulation reflects rapid dipeptidyl peptidase-4 (DPP-4) cleavage at the Tyr1-Ala2 bond.
Modified GRF 1-29 (CJC-1295 without DAC)
Modified GRF 1-29 carries four substitutions relative to sermorelin — most importantly D-Ala at position 2, which blocks the DPP-4 cleavage site. It is listed under CAS 863288-34-0, C152H252N44O42, MW 3367.9 Da. Note that it is the same peptide backbone as CJC-1295 with DAC, minus the albumin-binding attachment.
CJC-1295 with DAC
CJC-1295 with DAC adds an N-ε-maleimidopropionyl group to Lys30. That maleimide reacts covalently with a free cysteine thiol on circulating serum albumin, tethering the peptide to a long-lived carrier protein. The conjugate is described under CAS 446262-90-4, C165H269N47O46, MW 3647.3 Da. Teichman and colleagues reported sustained elevation of GH and IGF-I after single administration in healthy adults, and Ionescu and Frohman subsequently reported that GH pulsatility was preserved despite continuous receptor occupancy.
Tesamorelin
Tesamorelin is the full 44-residue GRF sequence bearing a trans-3-hexenoyl group on the N-terminal tyrosine (CAS 218949-48-5, C221H366N72O67S, MW 5135.9 Da). It is the only GHRH analogue in this group with a published phase 3 programme: Falutz and colleagues reported reductions in visceral adipose tissue in a randomised trial in people with HIV-associated lipodystrophy (New England Journal of Medicine, 2007). That work is cited here as research context only.
Family 2: GHRPs and the ghrelin receptor
Growth hormone-releasing peptides are short synthetic sequences, typically penta- or hexapeptides, that activate GHS-R1a. They were discovered by reverse pharmacology: Bowers and colleagues built them from opioid-peptide fragments in the 1980s, a decade before either the receptor or its natural ligand was known.
All four GHRPs stocked in the growth-hormone research category share a common design logic — D-amino acids and unnatural residues at positions vulnerable to peptidases, a C-terminal amide, and an aromatic cluster that occupies the receptor’s hydrophobic pocket.
Ipamorelin
Ipamorelin is the pentapeptide Aib-His-D-2-Nal-D-Phe-Lys-NH2 (CAS 170851-70-4, C38H49N9O5, MW 711.9 Da) and the smallest compound in this guide. Raun and colleagues characterised it in 1998 as the first GHS whose GH-releasing potency in rodent and swine models was not accompanied by the adrenocorticotropic hormone and prolactin responses seen with earlier GHRPs.
GHRP-2 (pralmorelin)
GHRP-2 is D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2 (CAS 158861-67-7, C45H55N9O6, MW 818.0 Da). It has been formulated as a single-administration diagnostic agent for assessment of GH deficiency in Japan, which makes it one of the better-documented GHRPs in the human literature.
GHRP-6
GHRP-6 is His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (CAS 87616-84-0, C46H56N12O6, MW 873.0 Da) — the original hexapeptide from the Bowers programme and the reference GHS-R1a ligand in much of the receptor-pharmacology literature. In rodent studies it is the GHRP most consistently reported to increase food intake, consistent with ghrelin mimicry at the arcuate nucleus.
Hexarelin (examorelin)
Hexarelin is His-2-Me-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (CAS 140703-51-1, C47H58N12O6, MW 887.1 Da), a 2-methylated GHRP-6 analogue. It is distinctive in the literature for reported binding to CD36 in cardiac tissue in addition to GHS-R1a, which is why it appears in cardiovascular preclinical work as well as somatotroph studies.
GHRH vs GHRP: side-by-side
The short answer: GHRH analogues raise the amplitude of GH pulses the hypothalamus already initiates, while GHRPs act partly by suppressing somatostatin tone and partly by direct somatotroph stimulation. Because the mechanisms are non-identical, the combined response in published pituitary and whole-animal work exceeds the arithmetic sum of the two alone.
| Compound | Family | Receptor | Structure | Distinguishing feature in the literature |
|---|---|---|---|---|
| Sermorelin | GHRH analogue | GHRH-R | GRF(1-29), unmodified | Reference fragment; DPP-4 sensitive at Tyr1-Ala2 |
| Mod GRF 1-29 (CJC-1295 no DAC) | GHRH analogue | GHRH-R | GRF(1-29) with D-Ala2 + 3 further substitutions | DPP-4-resistant backbone without albumin conjugation |
| CJC-1295 with DAC | GHRH analogue | GHRH-R | Same backbone + maleimidopropionyl-Lys30 | Covalent albumin binding; prolonged IGF-I elevation reported |
| Tesamorelin | GHRH analogue | GHRH-R | GRF(1-44) + trans-3-hexenoyl on Tyr1 | Only member with completed phase 3 trials |
| Ipamorelin | GHRP | GHS-R1a | Pentapeptide, C-terminal amide | Selectivity for GH over ACTH and prolactin in preclinical models |
| GHRP-2 (pralmorelin) | GHRP | GHS-R1a | Hexapeptide, D-Ala1/D-2-Nal2 | Used as a diagnostic GH-stimulation agent in Japan |
| GHRP-6 | GHRP | GHS-R1a | Hexapeptide, His1/D-Trp2 | Original Bowers hexapeptide; orexigenic in rodent studies |
| Hexarelin | GHRP | GHS-R1a (+ CD36) | 2-methyl-Trp2 GHRP-6 analogue | Reported cardiac CD36 binding independent of GHS-R1a |
Selectivity and off-target pituitary output
Selectivity within the GHRP family is the property that distinguishes ipamorelin from its predecessors. The somatotroph is not the only GHS-R1a-bearing cell in the anterior pituitary, and earlier hexapeptides were reported to raise adrenocorticotropic hormone, cortisol and prolactin alongside GH in preclinical work.
Raun and colleagues reported that ipamorelin released GH with potency comparable to GHRP-6 in their models while leaving those other axes substantially unaffected at GH-releasing concentrations. That is the specific claim that has kept ipamorelin in circulation as a research tool: it allows an experiment to attribute a downstream effect to the GH axis rather than to a generalised pituitary response.
GHRH analogues are inherently more selective because GHRH-R expression is largely confined to somatotrophs. The trade-off is that they cannot overcome high somatostatin tone, whereas GHRPs partly can.
Specifications: CAS, formula, molecular weight
Molecular weight is the practical number in this class, because it determines how many nanomoles a given mass contains. A 5 mg vial of ipamorelin (711.9 Da) holds roughly seven times more molecules than a 5 mg vial of tesamorelin (5135.9 Da) — a difference that matters for any molar-concentration assay.
| Compound | CAS | Molecular formula | MW (Da) | Residues |
|---|---|---|---|---|
| Sermorelin | 86168-78-7 | C149H246N44O42S | 3357.9 | 29 |
| Mod GRF 1-29 | 863288-34-0 | C152H252N44O42 | 3367.9 | 29 |
| CJC-1295 with DAC | 446262-90-4 | C165H269N47O46 | 3647.3 | 30 + linker |
| Tesamorelin | 218949-48-5 | C221H366N72O67S | 5135.9 | 44 + acyl |
| Ipamorelin | 170851-70-4 | C38H49N9O5 | 711.9 | 5 |
| GHRP-2 | 158861-67-7 | C45H55N9O6 | 818.0 | 6 |
| GHRP-6 | 87616-84-0 | C46H56N12O6 | 873.0 | 6 |
| Hexarelin | 140703-51-1 | C47H58N12O6 | 887.1 | 6 |
Handling, reconstitution and storage
All eight compounds ship as lyophilised powder and are reconstituted in the laboratory before assay. The concentrations below are a reference for preparing stock solutions for in-vitro and analytical work — they are not, and must not be read as, an amount for administration to any person or animal.
- Equilibrate. Bring the sealed vial to room temperature before opening to avoid condensation on the cake.
- Add diluent slowly. Direct the stream of bacteriostatic water down the vial wall rather than onto the lyophilised cake; peptides in this class are surface-active and foam readily.
- Dissolve by swirling. Do not vortex. Mechanical shear and air-liquid interface exposure both promote aggregation.
- Inspect. A correctly reconstituted solution is clear and colourless with no visible particulates.
- Aliquot. Divide into single-use volumes to avoid repeated freeze-thaw of the working stock.
- Record. Log batch number, diluent, date and resulting concentration against the vial’s certificate of analysis.
| Mass in vial | Diluent added | Resulting concentration | Amount per 0.1 mL | Ipamorelin molarity (MW 711.9) |
|---|---|---|---|---|
| 2 mg | 1 mL | 2 mg/mL | 200 mcg | 2.81 mM |
| 2 mg | 2 mL | 1 mg/mL | 100 mcg | 1.40 mM |
| 5 mg | 1 mL | 5 mg/mL | 500 mcg | 7.02 mM |
| 5 mg | 2 mL | 2.5 mg/mL | 250 mcg | 3.51 mM |
| 5 mg | 3 mL | 1.67 mg/mL | 167 mcg | 2.34 mM |
| 10 mg | 2 mL | 5 mg/mL | 500 mcg | 7.02 mM |
| 10 mg | 3 mL | 3.33 mg/mL | 333 mcg | 4.68 mM |
Limitations of the published evidence
The evidence base for this class is uneven. Tesamorelin has completed randomised phase 3 trials; GHRP-2 has a defined diagnostic role in one jurisdiction; ipamorelin, hexarelin and CJC-1295 have published human pharmacology but no completed late-phase programme for any indication.
A second limitation is the gap between acute GH release and any durable outcome. Demonstrating a GH pulse after a secretagogue is straightforward; demonstrating that repeated pulses produce a stable physiological change is a different and much harder experiment, and most of the published work stops at the first step.
Third, ghrelin-receptor biology has expanded considerably since 1999. GHS-R1a shows high constitutive activity and heterodimerises with other receptors, and the truncated GHS-R1b isoform does not signal conventionally — complications that any receptor-level study using GHRPs should account for.
Growth hormone secretagogues in the GenoPept store
Frequently asked questions
What is the difference between a GHRH analogue and a GHRP?
A GHRH analogue is a modified fragment of growth hormone-releasing hormone that binds the GHRH receptor and signals through Gs and cAMP. A GHRP is a small synthetic peptide, structurally unrelated to GHRH, that binds the ghrelin receptor GHS-R1a and signals through Gq and intracellular calcium. Both increase pituitary GH release, but by separate second-messenger routes.
Is CJC-1295 the same as Modified GRF 1-29?
Not quite. Both share the same tetrasubstituted GRF(1-29) backbone. CJC-1295 with DAC additionally carries a maleimidopropionyl group on Lys30 that binds covalently to serum albumin, giving CAS 446262-90-4 and MW 3647.3 Da. Modified GRF 1-29 lacks that group and is listed under CAS 863288-34-0 with MW 3367.9 Da.
Why is ipamorelin described as selective?
Raun and colleagues reported in 1998 that ipamorelin released growth hormone in rodent and swine models with potency comparable to GHRP-6, but without the accompanying rises in adrenocorticotropic hormone and prolactin that earlier growth hormone-releasing peptides produced. That separation of pituitary outputs is what the term selectivity refers to in this literature.
Do growth hormone secretagogues need to be refrigerated?
Lyophilised vials are typically held at −20 °C for long-term storage and are stable for shorter periods at 2–8 °C. Once reconstituted, solutions are refrigerated and protected from light. Tryptophan-containing GHRPs such as GHRP-6 and hexarelin are photolabile, so amber or foil-wrapped vessels are preferred for working stocks.
Why are GHRH analogues and GHRPs often studied together?
Because they occupy different receptors on the same cell. In published pituitary and whole-animal work, combining a GHRH-receptor agonist with a GHS-R1a agonist produces a larger growth hormone response than either compound alone, and the combination is used experimentally to probe whether an effect depends on one pathway or both.
What is the ghrelin receptor and when was it identified?
GHS-R1a is a class A G-protein-coupled receptor cloned by Howard and colleagues in 1996 from pituitary and hypothalamus. It was an orphan receptor at that point. Its natural ligand, the octanoylated stomach peptide ghrelin, was identified by Kojima and colleagues in 1999 and published in Nature.
How does molecular weight affect stock solution preparation?
Molar concentration depends on molecular weight, so equal masses of different secretagogues give very different molarities. At 1 mg/mL, ipamorelin (711.9 Da) is approximately 1.40 mM while tesamorelin (5135.9 Da) is approximately 0.19 mM. Assays specified in nM or µM require the calculation to be done per compound.
Are these compounds the same as somatropin?
No. Somatropin is recombinant human growth hormone itself — a 191-amino-acid protein of roughly 22 kDa. Secretagogues are much smaller peptides that act upstream on the pituitary to increase release of endogenous growth hormone. Somatropin bypasses that regulation entirely; secretagogues remain subject to it.
References
- Bowers CY, Momany FA, Reynolds GA, Hong A. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology. 1984;114(5):1537–1545. Endocrinology
- Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974–977. PubMed
- Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–660. PubMed
- Raun K, Hansen BS, et al. Ipamorelin, the first selective growth hormone secretagogue. European Journal of Endocrinology. 1998;139(5):552–561. PubMed
- Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. The Journal of Clinical Endocrinology & Metabolism. 2006;91(3):799–805. PubMed
- Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. The Journal of Clinical Endocrinology & Metabolism. 2006;91(12):4792–4797. PubMed
- Falutz J, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine. 2007;357(23):2359–2370. PubMed
- Steyn FJ, Tolle V, Chen C, Epelbaum J. Neuroendocrine regulation of growth hormone secretion. Comprehensive Physiology. 2016;6(2):687–735. Wiley
Research-grade growth hormone secretagogues, batch-verified
GenoPept supplies sermorelin, tesamorelin, CJC-1295 (with and without DAC), ipamorelin, GHRP-2, GHRP-6 and hexarelin as lyophilised vials with a per-batch third-party certificate of analysis covering HPLC purity and mass confirmation, dispatched from the UK strictly for laboratory research.