What are growth hormone secretagogues?
A secretagogue is a substance that makes a gland secrete. Growth hormone secretagogues, or GH secretagogues, make the pituitary release its own growth hormone (GH) rather than supplying the hormone. In the narrow sense, the name covers small synthetic molecules that release GH through their own receptor, GHS-R, separate from the pathway of hypothalamic growth hormone-releasing hormone (GHRH) (Kojima et al., 1999).
In the broad sense GHRH counts too: Merck's 1995 MK-677 paper calls it the natural GH secretagogue (Patchett et al., 1995), so the term spans two families: GHRH analogs and ghrelin mimetics. Disguised Alpha supplies sermorelin, CJC-1295 with and without DAC, tesamorelin and ipamorelin as lyophilized powders, and MK-677 as capsules, for laboratory research use only. Nothing on this page is guidance for use in people.
The growth hormone axis
GH comes from somatotrophs in the anterior pituitary, and two hypothalamic peptides set their output. GHRH drives release through a receptor expressed predominantly in the anterior pituitary (Mayo, 1992). Somatostatin holds it back: the 14-residue peptide, isolated from sheep hypothalamus in 1973, inhibited GH secretion in vitro and in rats (Brazeau et al., 1973). GH promotes production of insulin-like growth factor 1 (IGF-1) (Dominikowski et al., 2026), and IGF-1 feeds back.
In rat tissue, it raised hypothalamic somatostatin release within 20 minutes and, after 24 hours, cut stimulated GH release from pituitary cells by more than 90 percent (Berelowitz et al., 1981). Ghrelin, a 28-residue acylated stomach peptide identified in 1999, is a third input (Kojima et al., 1999). IGF-1 LR3 acts downstream at the IGF-1 receptor and is not a secretagogue (Dominikowski et al., 2026; see the IGF-1 LR3 guide).
Two receptors: GHRH analogs vs ghrelin mimetics
GHRH analogs act at the GHRH receptor. The cloned human receptor bound GHRH with high affinity, and GHRH raised cyclic AMP in cells carrying it (Mayo, 1992). Ghrelin mimetics act at the growth hormone secretagogue receptor, GHS-R1a, which Merck scientists cloned in 1996 from pig and human pituitary and hypothalamus; they proposed that the synthetic secretagogues mimic an undiscovered hormone (Howard et al., 1996).
Ghrelin proved to be that hormone (Kojima et al., 1999), hence the name ghrelin mimetics. The pathways are separate: in rat pituitary cells, GHRP-6 released GH without raising cyclic AMP, GHRH raised it about three fold, and a GHRH antagonist did not block GHRP-6 (Cheng et al., 1989).
The GHRH analog family
Native human GHRH has 44 residues (Ferdinandi et al., 2007), and the GHRH analog peptides below each modify it differently.
- Sermorelin is the GHRH(1-29) fragment. As the drug product Geref, it was FDA approved in 1990 as a pituitary GH test and in 1997 for idiopathic GH deficiency in children. The maker discontinued it in 2008, and the approvals were withdrawn at its request in 2009 (Federal Register, 2013; Dominikowski et al., 2026).
- CJC-1295 keeps residues 1 to 29 with four substitutions that resist enzymatic breakdown, and CJC-1295 with DAC adds a group that binds circulating albumin (Dominikowski et al., 2026). In placebo-controlled trials in healthy adults, its estimated half-life was 5.8 to 8.1 days, and one exposure raised mean GH for six days or more (Teichman et al., 2006).
- CJC-1295 No DAC, also sold as modified GRF 1-29, lacks that group and has no peer-reviewed human studies or reported human half-life (Dominikowski et al., 2026). See CJC-1295 DAC vs No DAC.
- Tesamorelin keeps all 44 residues and adds a trans-3-hexenoyl group to tyrosine 1, which resisted dipeptidyl aminopeptidase-IV and slowed breakdown in rat, dog and human plasma (Ferdinandi et al., 2007). A tesamorelin drug product was approved in the United States in November 2010 for one HIV-related indication (Dominikowski et al., 2026); the research material sold here is not that product. See tesamorelin vs CJC-1295.
The ghrelin mimetic family
Ghrelin mimetics existed before ghrelin was known. GHRP-6, the hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, released GH in 18 normal men, with prolactin and cortisol rising only at the highest amount tested (Bowers et al., 1990). It was the first hexapeptide studied extensively in humans; GHRP-1, GHRP-2 and hexarelin followed, as did non-peptide mimetics such as MK-0677 that act through the same receptor (Ghigo et al., 1997).
These secretagogue peptides are not fully selective: GHRP-6 and GHRP-2 raised ACTH and cortisol in swine (Raun et al., 1998), and human studies report prolactin and cortisol rises with GHRP-2 and hexarelin (Dominikowski et al., 2026). Disguised Alpha does not carry these three; they appear here as research history.
Ipamorelin, the pentapeptide Aib-His-D-2-Nal-D-Phe-Lys-NH2, was described in 1998 as the first selective GH secretagogue. About as potent as GHRP-6 in rat pituitary cells, rats and swine, it did not raise ACTH or cortisol in swine beyond the levels seen with GHRH (Raun et al., 1998). MK-677 (ibutamoren, MK-0677) is not a peptide (Ghigo et al., 1997). Merck described a compound that released GH from rat pituitary cells, acted like GHRP-6 rather than GHRH, and raised GH in dogs given it by mouth (Patchett et al., 1995).
GHRH analogs vs ghrelin mimetics at a glance
| Compound | Class | Receptor | Form studied | Our guide |
|---|---|---|---|---|
| Sermorelin | GHRH analog | GHRH receptor | Peptide, GHRH(1-29) | Sermorelin guide |
| CJC-1295 No DAC | GHRH analog | GHRH receptor | Peptide, substituted GHRH(1-29); no peer-reviewed human studies | CJC-1295 No DAC guide |
| CJC-1295 with DAC | GHRH analog | GHRH receptor | Peptide, substituted GHRH(1-29) plus an albumin-binding group | CJC-1295 with DAC guide |
| Tesamorelin | GHRH analog | GHRH receptor | Peptide, GHRH(1-44) with an N-terminal hexenoyl group | Tesamorelin guide |
| GHRP-6 | Ghrelin mimetic (GHRP) | GHS-R1a | Hexapeptide | GHRP-6 guide |
| GHRP-2 | Ghrelin mimetic (GHRP) | GHS-R1a | Hexapeptide | GHRP-2 guide |
| Hexarelin | Ghrelin mimetic (GHRP) | GHS-R1a | Hexapeptide | Hexarelin guide |
| Ipamorelin | Ghrelin mimetic | GHS-R1a | Pentapeptide | Ipamorelin guide |
| MK-677 (ibutamoren) | Ghrelin mimetic, non-peptide | GHS-R1a | Small molecule, active by mouth | MK-677 guide |
Form studied: the molecule used in the cited work.
Why researchers pair one of each
With separate receptors and signals, one of each can release more GH than either alone. In rat pituitary cells, GHRP-6 and GHRH at maximal concentrations had a synergistic effect on GH release, and GHRP-6 amplified the cyclic AMP rise caused by GHRH. Pretreatment with GHRP-6 dulled a later response to GHRP-6 but not to GHRH (Cheng et al., 1989).
In 18 normal men, submaximal amounts of GHRP-6 with GHRH released GH synergistically, which the authors read as the two acting independently (Bowers et al., 1990). Part of the explanation is hypothalamic. GHRP peptides act at both pituitary and hypothalamus, may work partly by opposing somatostatin and partly through GHRH, and barely release GH in people with pituitary stalk disconnection (Ghigo et al., 1997).
These studies used GHRP-6 and unmodified GHRH, not catalog compounds. A PubMed search in October 2026 found no experimental study of CJC-1295 or tesamorelin with ipamorelin, and a 2026 review called controlled evidence for synergy in the CJC-1295 and ipamorelin pairing limited (Dominikowski et al., 2026). Testing synergy needs four arms: vehicle, each compound alone and both together. See CJC-1295 vs ipamorelin, tesamorelin vs ipamorelin and the blend guides for CJC-1295 No DAC with ipamorelin and tesamorelin with ipamorelin.
Pulsatility and somatostatin tone
GH is released in pulses. When six healthy young men received a constant 24-hour GHRH infusion, GH secretion stayed pulsatile and natural pulses grew larger. The authors proposed that each pulse reflects GHRH release coupled with a fall in somatostatin (Vance et al., 1985). Somatostatin tone, the inhibitory background, therefore gates when somatotrophs can respond, and IGF-1 feedback raises it (Berelowitz et al., 1981). Both classes work inside this system.
Secretagogues amplify pulsatile GH release (Howard et al., 1996). GHRH analog effects stay shaped by somatostatin tone and IGF-1 feedback, though long-acting forms such as CJC-1295 with DAC give more sustained stimulation (Dominikowski et al., 2026). GHRP responses partly desensitize, more under continuous infusion than with intermittent exposure (Ghigo et al., 1997). A single GH sample can land on a peak or a trough, so sampling frequency shapes what a study detects.
Regulatory and anti-doping status
Among the GHRH analogs here, only tesamorelin is part of a currently approved US drug product, and neither form of CJC-1295 has been approved by the FDA or the EMA (Dominikowski et al., 2026). GHRP-2, as pralmorelin, has a diagnostic role in Japan (Dominikowski et al., 2026).
An FDA page on bulk drug substances that may present significant safety risks places GHRP-2 (for certain routes), GHRP-6, ibutamoren mesylate and ipamorelin acetate in category 2 of its compounding interim policies. It lists CJC-1295 among substances whose nominations were withdrawn. The 2026 WADA Prohibited List names GHRH and its analogues (e.g. CJC-1295, sermorelin, tesamorelin), GH secretagogues and their mimetics (e.g. ibutamoren, ipamorelin, ghrelin) and GH-releasing peptides (e.g. GHRP-2, GHRP-6, hexarelin) under S2.2.4, in class S2, which is prohibited at all times.
Key sources
- Kojima M, et al. Nature. 1999. PMID 10604470. Ghrelin, the secretagogue receptor ligand.
- Cheng K, et al. Endocrinology. 1989. PMID 2541999. Rat pituitary cells: synergy and cyclic AMP.
- Bowers CY, et al. J Clin Endocrinol Metab. 1990. PMID 2108187. Normal men: GHRP-6 and GHRH synergy.
- Vance ML, et al. J Clin Invest. 1985. PMID 2860126. Pulsatile GH during constant GHRH infusion.
- Dominikowski A, et al. Front Endocrinol. 2026. PMID 42395176. Review of GH axis peptides and their status.
Frequently asked questions
What are growth hormone secretagogues?
Compounds that make the pituitary release its own growth hormone: GHRH analogs, acting at the GHRH receptor, and ghrelin mimetics, acting at GHS-R1a (Kojima et al., 1999).
What is the difference between GHRH analogs and ghrelin mimetics?
Different receptors and signals. In rat pituitary cells GHRH raised cyclic AMP and GHRP-6 did not, yet together they released more GH than either alone (Cheng et al., 1989).
What are GHRP peptides?
Growth hormone-releasing peptides: GHRP-1, GHRP-6, GHRP-2 and hexarelin, synthetic peptides developed before ghrelin was discovered (Ghigo et al., 1997). Disguised Alpha lists hexarelin but not the others. The GHRP-6, GHRP-2 and hexarelin guides cover what studies of each measured.
Is MK-677 a secretagogue peptide?
No. MK-677 (ibutamoren) is a non-peptide that acts like GHRP-6 rather than GHRH (Ghigo et al., 1997; Patchett et al., 1995).
Why are CJC-1295 and ipamorelin studied together?
One is a GHRH analog and the other a ghrelin mimetic, and GHRH with GHRP-6 released GH synergistically in normal men (Bowers et al., 1990). The pairing itself has no published experimental study.
Which GH secretagogues does Disguised Alpha carry?
Sermorelin Acetate, CJC-1295 No DAC, CJC-1295 Drug Affinity Complex, Tesamorelin, Ipamorelin, MK-677 (Ibutamoren), plus two blends, for laboratory research only, with lot certificates in the COA portal.
Related guides
- CJC-1295 DAC vs No DAC
- CJC-1295 vs Ipamorelin
- Tesamorelin vs Ipamorelin
- Tesamorelin vs CJC-1295
- IGF-1 LR3 research guide
- What is a peptide?
- Research hub
Disguised Alpha products are for research use only. They have not been evaluated for safety or effectiveness in humans. Not for human consumption. All products are intended for laboratory research purposes only.