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GHRH (1-29)

Also known as: Sermorelin, GHRH(1-29)NH2, [Nle27]GHRH(1-29)-NH2, hGRF(1-29), GH-RH 1-29, Growth Hormone-Releasing Hormone (1-29), Somatocrinin (1-29 fragment)

Hypothalamic neuropeptide / GH secretagogue (endogenous peptide fragment and synthetic analogue)

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What it is

GHRH (1-29) is the biologically active N-terminal fragment of hypothalamic growth hormone-releasing hormone. It binds to pituitary-type GHRH receptors (pGHRH-R) and their splice variants (principally SV1) on pituitary somatotrophs, stimulating GH secretion. The receptor is a G-protein-coupled receptor (GPCR) whose activation elevates intracellular cAMP. In extrapituitary tissues, autocrine/paracrine GHRH and its receptors are expressed in a wide variety of cancer cell lines, where GHRH promotes proliferation, angiogenesis, and survival via downstream pathways including ERK1/2 MAPK, JAK2/STAT3, NF-κB, and Akt/mTOR. GH release then stimulates hepatic IGF-I production, which mediates many anabolic and growth-promoting effects. GHRH also modulates immune function; lymphocytes express GHRH and its receptors, and GHRH administration enhances immune cell activity in aging individuals. Antagonists of GHRH block pGHRH-R and SV1, suppressing tumor growth, inducing autophagy and apoptosis, and exerting anti-inflammatory effects.

Class: Hypothalamic neuropeptide / GH secretagogue (endogenous peptide fragment and synthetic analogue)

What it's studied for

  • Stimulation of GH secretion / GH deficiency testing Human RCT
    • IV bolus GHRH(1-29)NH2 at 0.05, 0.15, and 1.0 µg/kg in post-irradiation GH-insufficient adults and matched controls; GH response was significantly attenuated in irradiated subjects at physiological doses, with incremental rises at higher doses reflecting reduced pituitary responsiveness. PMID 10754477 Achermann JC et al. Eur J Endocrinol (2000)
    • IV bolus GHRH(1-29)NH2 at 1, 10, and 100 µg doses in 10 adult male volunteers; 10 and 100 µg doses produced significant peak GH responses (~24–26 mU/l); dose-dependent delays in time-to-peak GH and prolongation of GH elevation were observed. PMID 7921207 Spoudeas HA et al. Eur J Endocrinol (1994)
    • IV doses as low as 0.25 µg/kg elicited significant GH release; maximal release (mean ~90 mU/l) achieved with 1–2 µg/kg IV. Intranasal bioavailability was 3–5%; maximal intranasal GH response required ~50 µg/kg. PMID 8329825 Wilton P et al. Acta Paediatrica Suppl (1993)
    • 3-hour escalating IV infusion of GHRH(1-29) (0.2, 0.4, 0.6 µg/kg/h) plus 2 µg/kg IV bolus in 29 hypopituitary patients; GH response varied markedly by MRI-defined pituitary morphology, supporting its use for differential diagnosis. PMID 8810733 Maghnie M et al. Eur J Endocrinol (1996)
  • Treatment of growth hormone deficiency and growth promotion in children Human RCT
    • 110 GH-deficient prepubertal children received GHRH-(1-29) 30 µg/kg/day SC at bedtime for up to 1 year; mean height velocity increased from 4.1 cm/yr at baseline to 8.0 cm/yr at 6 months and 7.2 cm/yr at 12 months; well tolerated with no adverse biochemical changes. PMID 8772599 Thorner M et al. J Clin Endocrinol Metab (1996)
    • 18 short prepubertal children received GHRH(1-29)NH2 20 µg/kg twice-daily SC for 12 months; height velocity increased from 4.8 to 7.2 cm/yr; fasting glucose and insulin rose; catch-down growth occurred in the first 3 months post-discontinuation. PMID 7955460 Kirk JM et al. Clin Endocrinol (1994)
    • 9 children with radiation-induced GH deficiency received GHRH(1-29)-NH2 15 µg/kg twice-daily SC; height velocity increased from 3.3 to 6.0 cm/yr after 1 year (P=0.004); no adverse biochemical events attributed to GHRH. PMID 9231053 Ogilvy-Stuart AL et al. Clin Endocrinol (1997)
    • 16 children with idiopathic short stature and 8 with GH neurosecretory dysfunction received GHRH 1-29 30 µg/kg SC nightly for 6 months; both groups had similar significant growth rate increases; rates returned to pre-therapy levels 6 months after discontinuation. PMID 10905389 Schwartz ID et al. J Pediatr Endocrinol Metab (2000)
    • 43 prepubertal GH-deficient children randomized to GHRH(1-29)-NH2 30 µg/kg/day SC (low dose), 60 µg/kg/day SC (high dose), or GH 0.1 IU/kg/day SC for 6 months; height velocity comparable between high-dose GHRH and GH groups; GHRH antibodies developed in most GHRH-treated patients. PMID 8329826 Neyzi O et al. Acta Paediatrica Suppl (1993)
  • Restoration of GH/IGF-I axis in aging men and women Human RCT
    • 19 men and women aged 55–71 yr received [Nle27]GHRH(1-29)-NH2 10 µg/kg SC nightly for 16 weeks; significant increases in nocturnal GH, IGF-I, and IGFBP-3; lean body mass increased in men; transient hyperlipidemia was the only adverse effect. PMID 9141536 Khorram O et al. J Clin Endocrinol Metab (1997)
    • 10 healthy older men received GHRH-(1-29) 0.5 mg or 1 mg SC twice daily for 14 days; dose-related increases in 24-h GH and IGF-I; high dose restored parameters to young-men levels; no effect on fasting glucose or blood pressure. PMID 1379256 Corpas E et al. J Clin Endocrinol Metab (1992)
    • 11 healthy men aged 64–76 yr received 2 mg GHRH SC nightly for 6 weeks; nocturnal GH release and GH peak amplitude increased; two of six muscle strength measures improved; no change in body composition by DEXA or lipids; no significant adverse effects. PMID 9005976 Vittone J et al. Metabolism (1997)
  • Immunomodulation in aging Human RCT
    • Healthy elderly subjects (10 women, 9 men) self-administered [Nle27]GHRH(1-29)-NH2 10 µg/kg SC nightly for 16 weeks; significant increases in B cells, T cell receptor subsets, lymphocyte proliferative responses, IL-2R expression, and basal IL-2 secretion; no sex differences in immune response; no adverse effects report PMID 9360512 Khorram O et al. J Clin Endocrinol Metab (1997)
  • Differential diagnosis of hypothalamic vs. pituitary GH deficiency Human observational
    • GHRH(1-29)NH2 5 µg/kg SC for 6 consecutive days ('priming') in 16 short non-responders separated patients into hypothalamic-origin (responders after priming, n=8) vs. pituitary-origin (non-responders after priming, n=8) GH deficiency. PMID 7735368 Bueno G et al. J Pediatr Endocrinol (1994)
    • 3-hour GHRH(1-29) infusion protocol in 29 hypopituitary patients differentiated those with pituitary stalk abnormalities (very low GH response) from those with small anterior pituitary or normal pituitary morphology (higher GH responses). PMID 8810733 Maghnie M et al. Eur J Endocrinol (1996)
  • Pharmacokinetic / structure-activity research (agonist role) Mixed
    • Constant IV infusion of GHRH-(1-29)-NH2 at 25 ng/kg/min in 10 normal men; metabolic clearance rate 39.7 ± 3.9 mL/kg/min; disappearance half-time ~4.3 min; D-Ala2 substitution significantly reduced MCR and extended half-life. PMID 7962295 Soule S et al. J Clin Endocrinol Metab (1994)
    • Maleimido derivatives of hGRF(1-29) bioconjugated to human serum albumin showed enhanced stability against DPP-IV; CJC-1295, a tetrasubstituted hGRF(1-29) analog, achieved 4-fold greater GH AUC vs. native hGRF(1-29) and detectable plasma levels beyond 72 h in rats after SC administration. PMID 15817669 Jetté L et al. Endocrinology (2005)
    • Systematic alanine-scan and Aib-substitution SAR of [Nle27]-hGHRH(1-29)-NH2 identified residues critical for receptor activation; multiple-substitution and lactam-constrained analogues achieved up to 26-fold greater in vitro GH-releasing potency vs. hGHRH(1-40)-OH standard. PMID 9513600 Cervini LA et al. J Med Chem (1998)
  • Autocrine/paracrine growth factor in cancer (in vitro and animal models — agonist GHRH promotes tumor growth; used as comparator in antagonist studies) Mixed
    • GHRH(1-29)NH2 stimulated proliferation of H-69 and H-510A small cell lung carcinoma lines in vitro; GHRH mRNA and peptide were detected in SCLC conditioned media, supporting an autocrine growth factor role. PMID 10611309 Kiaris H et al. PNAS (1999)
    • GHRH(1-29)NH2 at 10⁻⁸–10⁻⁶ M increased proliferation of human bronchial neuroendocrine tumor cells NCI-H727 and stimulated VEGF and chromogranin A secretion in vitro. PMID 19747727 Stepień T et al. Neuropeptides (2009)
    • siRNA knockdown of GHRH suppressed proliferation of breast, prostate, and lung cancer cell lines in vitro; exogenous GHRH(1-29)NH2 re-established proliferation of silenced lines, confirming GHRH as a tumour growth factor. PMID 18506184 Barabutis N & Schally AV. Br J Cancer (2008)

Community-reported dosing

RouteDoseFrequency / DurationPopulation / contextSource tier
Subcutaneous injection, once daily at bedtime30 µg/kg/dayUp to 12 monthshumanResearch PMID 8772599
Subcutaneous injection20 µg/kg twice daily12 monthshumanResearch PMID 7955460
Subcutaneous injection15 µg/kg twice daily12 monthshumanResearch PMID 9231053
Subcutaneous injection30 µg/kg once nightly6 monthshumanResearch PMID 10905389
Subcutaneous self-injection10 µg/kg once nightly16 weeks (preceded by 4 weeks placebo)humanResearch PMID 9141536
Subcutaneous self-injection10 µg/kg once nightly16 weekshumanResearch PMID 9360512
Subcutaneous injection0.5 mg or 1 mg twice daily14 days per dose levelhumanResearch PMID 1379256
Subcutaneous self-injection2 mg once nightly6 weekshumanResearch PMID 9005976
Intravenous bolus1 µg, 10 µg, or 100 µg IV bolus (approximately 0.01–1.5 µg/kg for median 68 kg subjects)Single dose (dose-response study)humanResearch PMID 7921207
Intravenous bolus0.05 µg/kg, 0.15 µg/kg, or 1.0 µg/kgSingle dose per occasion (randomised crossover)humanResearch PMID 10754477
Intravenous and intranasal0.25–2 µg/kg IV; 50 µg/kg intranasalSingle dose (pharmacokinetic study); repeated intranasal (within-day)humanResearch PMID 8329825
Intravenous bolus1.0 µg/kg IV bolus (GHRH-(1-29)-NH2)Single dosehumanResearch PMID 9579235
Intravenous bolus400 µg/kg IV (GHRH antagonist); GHRH(1-29)NH2 used as reference comparatorSingle dosehumanResearch PMID 9543138
Intravenous infusion25 ng/kg/min constant IV infusion90 minutes infusion + 20 min washouthumanResearch PMID 7962295
Subcutaneous injection (three daily doses) or continuous subcutaneous infusion30 µg/kg/day (low dose) or 60 µg/kg/day (high dose) in three daily SC doses6 monthshumanResearch PMID 8329826
Continuous subcutaneous infusion (parenteral)30 µg/kg/day (low dose) or 60 µg/kg/day (high dose) continuous infusion6 monthshumanResearch PMID 8329830
Intranasal insufflation50 µg/kg three times daily intranasal6 monthshumanResearch PMID 8329828
Subcutaneous infusion60 ng/kg/min continuous SC infusion (24 h) for 'clamp' studies24 hours per clamp studyhumanResearch PMID 10594518
Subcutaneous (priming) and intravenous (test bolus)5 µg/kg SC daily for 6 days (priming); then 1 µg/kg IV bolus on day 77 dayshumanResearch PMID 7735368
Continuous subcutaneous infusionContinuous SC infusion (dose not fully specified in abstract; described as partial GH deficiency treatment cohort)6 monthshumanResearch PMID 8329829
Intravenous bolus100 µg IV bolusSingle dosehumanResearch PMID 8445152
Intravenous bolus1 µg/kg IV bolusSingle dosehumanResearch PMID 8622602
Intravenous infusion + bolus0.2 µg/kg/h (1 h), 0.4 µg/kg/h (1 h), 0.6 µg/kg/h (1 h) escalating infusion + 2 µg/kg IV bolusSingle 3-hour infusion sessionhumanResearch PMID 8810733
In vitro (cell culture)10⁻⁸–10⁻⁶ MNot specified (in vitro proliferation assay)in_vitroResearch PMID 19747727
Subcutaneous injection (rat)CJC-1295 (hGRF(1-29) bioconjugate) administered SC; dose not specified in abstract for rat studiesAcute (single dose pharmacokinetic study)animalResearch PMID 15817669
In vitro (primary cell culture)Not specified (in vitro primary pituitary cell co-incubation with GHRH and GHRH receptor antagonist acetyl-(d-Arg2)-GHRH(1-29) amide)Not specifiedin_vitroResearch PMID 26671997
subcutaneous injection100 mcgonce daily, pre-sleepbiohackers and fitness-oriented adults seeking GH pulse optimization[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection100 mcgtwice daily (morning fasted + pre-sleep)intermediate to advanced biohackers and gym-focused users running full GHRH+GHRP stacks[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection100 mcgthree times daily (morning fasted, post-workout, pre-sleep)advanced bodybuilders and biohackers maximizing GH release throughout the day[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection100 mcgonce daily, pre-sleepadults 40+ using peptides for anti-aging and longevity[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection100 mcgonce daily, pre-sleep, 5 days on / 2 days offbiohackers concerned about pituitary desensitization on extended runs[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection100 mcgonce daily, pre-sleepathletes and gym users for soft-tissue injury recovery[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection100 mcgonce daily, pre-sleeppost-cycle (anabolic steroid) users seeking hormonal restoration and body recomposition[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection100 mcgonce daily, 45-60 minutes pre-workout (fasted or 2+ hours post-meal)performance-focused athletes and gym users[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection50 mcgonce daily, pre-sleeppeptide beginners or those sensitive to GH-related side effects[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection200 mcgonce to twice dailyadvanced biohackers and bodybuilders seeking enhanced GH secretion beyond standard doses[S] Claude Sonnet 4.6 — synthesized from aggregate training data
subcutaneous injection100 mcgonce daily, pre-sleepadults using peptides primarily for sleep quality improvement[S] Claude Sonnet 4.6 — synthesized from aggregate training data

Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.

References

  1. [1] PMID 10754477 — IV bolus GHRH(1-29)NH2 at 0.05, 0.15, and 1.0 µg/kg in post-irradiation GH-insufficient adults and matched controls; GH response was significantly attenuated in
  2. [2] PMID 7921207 — IV bolus GHRH(1-29)NH2 at 1, 10, and 100 µg doses in 10 adult male volunteers; 10 and 100 µg doses produced significant peak GH responses (~24–26 mU/l); dose-de
  3. [3] PMID 8329825 — IV doses as low as 0.25 µg/kg elicited significant GH release; maximal release (mean ~90 mU/l) achieved with 1–2 µg/kg IV. Intranasal bioavailability was 3–5%;
  4. [4] PMID 8810733 — 3-hour escalating IV infusion of GHRH(1-29) (0.2, 0.4, 0.6 µg/kg/h) plus 2 µg/kg IV bolus in 29 hypopituitary patients; GH response varied markedly by MRI-defin
  5. [5] PMID 8772599 — 110 GH-deficient prepubertal children received GHRH-(1-29) 30 µg/kg/day SC at bedtime for up to 1 year; mean height velocity increased from 4.1 cm/yr at baselin
  6. [6] PMID 7955460 — 18 short prepubertal children received GHRH(1-29)NH2 20 µg/kg twice-daily SC for 12 months; height velocity increased from 4.8 to 7.2 cm/yr; fasting glucose and
  7. [7] PMID 9231053 — 9 children with radiation-induced GH deficiency received GHRH(1-29)-NH2 15 µg/kg twice-daily SC; height velocity increased from 3.3 to 6.0 cm/yr after 1 year (P
  8. [8] PMID 10905389 — 16 children with idiopathic short stature and 8 with GH neurosecretory dysfunction received GHRH 1-29 30 µg/kg SC nightly for 6 months; both groups had similar
  9. [9] PMID 8329826 — 43 prepubertal GH-deficient children randomized to GHRH(1-29)-NH2 30 µg/kg/day SC (low dose), 60 µg/kg/day SC (high dose), or GH 0.1 IU/kg/day SC for 6 months;
  10. [10] PMID 9141536 — 19 men and women aged 55–71 yr received [Nle27]GHRH(1-29)-NH2 10 µg/kg SC nightly for 16 weeks; significant increases in nocturnal GH, IGF-I, and IGFBP-3; lean
  11. [11] PMID 1379256 — 10 healthy older men received GHRH-(1-29) 0.5 mg or 1 mg SC twice daily for 14 days; dose-related increases in 24-h GH and IGF-I; high dose restored parameters
  12. [12] PMID 9005976 — 11 healthy men aged 64–76 yr received 2 mg GHRH SC nightly for 6 weeks; nocturnal GH release and GH peak amplitude increased; two of six muscle strength measure
  13. [13] PMID 9360512 — Healthy elderly subjects (10 women, 9 men) self-administered [Nle27]GHRH(1-29)-NH2 10 µg/kg SC nightly for 16 weeks; significant increases in B cells, T cell re
  14. [14] PMID 7735368 — GHRH(1-29)NH2 5 µg/kg SC for 6 consecutive days ('priming') in 16 short non-responders separated patients into hypothalamic-origin (responders after priming, n=
  15. [15] PMID 7962295 — Constant IV infusion of GHRH-(1-29)-NH2 at 25 ng/kg/min in 10 normal men; metabolic clearance rate 39.7 ± 3.9 mL/kg/min; disappearance half-time ~4.3 min; D-Ala
  16. [16] PMID 15817669 — Maleimido derivatives of hGRF(1-29) bioconjugated to human serum albumin showed enhanced stability against DPP-IV; CJC-1295, a tetrasubstituted hGRF(1-29) analo
  17. [17] PMID 9513600 — Systematic alanine-scan and Aib-substitution SAR of [Nle27]-hGHRH(1-29)-NH2 identified residues critical for receptor activation; multiple-substitution and lact
  18. [18] PMID 10611309 — GHRH(1-29)NH2 stimulated proliferation of H-69 and H-510A small cell lung carcinoma lines in vitro; GHRH mRNA and peptide were detected in SCLC conditioned medi
  19. [19] PMID 19747727 — GHRH(1-29)NH2 at 10⁻⁸–10⁻⁶ M increased proliferation of human bronchial neuroendocrine tumor cells NCI-H727 and stimulated VEGF and chromogranin A secretion in
  20. [20] PMID 18506184 — siRNA knockdown of GHRH suppressed proliferation of breast, prostate, and lung cancer cell lines in vitro; exogenous GHRH(1-29)NH2 re-established proliferation
  21. [21] PMID 9579235 — 1.0 µg/kg IV bolus (GHRH-(1-29)-NH2) Intravenous bolus (human)
  22. [22] PMID 9543138 — 400 µg/kg IV (GHRH antagonist); GHRH(1-29)NH2 used as reference comparator Intravenous bolus (human)
  23. [23] PMID 8329830 — 30 µg/kg/day (low dose) or 60 µg/kg/day (high dose) continuous infusion Continuous subcutaneous infusion (parenteral) (human)
  24. [24] PMID 8329828 — 50 µg/kg three times daily intranasal Intranasal insufflation (human)
  25. [25] PMID 10594518 — 60 ng/kg/min continuous SC infusion (24 h) for 'clamp' studies Subcutaneous infusion (human)
  26. [26] PMID 8329829 — Continuous SC infusion (dose not fully specified in abstract; described as partial GH deficiency treatment cohort) Continuous subcutaneous infusion (human)
  27. [27] PMID 8445152 — 100 µg IV bolus Intravenous bolus (human)
  28. [28] PMID 8622602 — 1 µg/kg IV bolus Intravenous bolus (human)
  29. [29] PMID 26671997 — Not specified (in vitro primary pituitary cell co-incubation with GHRH and GHRH receptor antagonist acetyl-(d-Arg2)-GHRH(1-29) amide) In vitro (primary cell cul
  30. [30] PMID 32289177 — in-prose reference
  31. [31] PMID 12186980 — in-prose reference
  32. [32] PMID 31611400 — in-prose reference
  33. [33] PMID 41075421 — in-prose reference
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