GH Fragment 176-191
Also known as: HGH Frag 176-191, HGH Fragment 176-191, hGH(176-191)
Evidence: Preclinical
Overview
Synthetic C-terminal fragment of human growth hormone (residues 176-191). Related fragments cut fat gain in obese rodents; the one study of 176-191 itself found a brief rise in blood glucose in rats.
GH Fragment 176-191 is the last 16 residues of human growth hormone, FLRIVQCRSVEGSCGF. Monash University work from the 1970s on found that C-terminal hGH fragments affect fat and glucose metabolism. In rats, hGH 176-191 and related fragments caused a short-lived rise in blood glucose and insulin, and fragments containing 178-191 reduced insulin sensitivity (Ng 1978). The shorter hGH 177-191 had antilipogenic activity in rat fat (Wu 1993) and reduced weight gain and fat mass in obese mice (Natera 1994). The tyrosine analog AOD9604 was the version taken forward; it did not alter glucose in rodents or humans (Heffernan 2001). No human study of hGH 176-191 itself exists. Products sold under this name often list the AOD9604 sequence.
Benefits
Antilipogenic activity (rat fat tissue, hGH 177-191), reduced weight gain and fat mass (obese mice, hGH 177-191), raised fat oxidation (obese mice, AOD9604 analog); no human data for this fragment
Dosing reference
- Research dose
- 250 to 500 mcg 2 to 3 times daily (vendor/community range, no published human dose)
- Range
- 250 to 500 mcg, 2x daily
- Reconstitution
- 2 mL bacteriostatic water
- Common vial sizes
- 5 mg
Community protocols inject subcutaneously, often fasted. No human dose of hGH 176-191 has been published; rodent work dosed by weight (5 nmol/kg IV in rats, Ng 1978). Human trials used the AOD9604 analog, orally or IV (Stier 2013).
Mechanism
The C-terminal region of hGH carries its lipolytic and antilipogenic activity. hGH 177-191 inhibited lipogenesis in rat adipose tissue without measurable lipolysis (Wu 1993); a 177-191 analog stimulated hormone-sensitive lipase and inhibited acetyl-CoA carboxylase in rat fat (Ng 2000, J Mol Endocrinol). The related AOD9604 does not bind the GH receptor (Heffernan 2001). For hGH 176-191 specifically, the only data show acute hyperglycaemic and insulin-raising effects in rats (Ng 1978), so a glucose-neutral profile is not established for this fragment. Beta-3-adrenergic involvement is not supported; AOD9604 acted independently of that receptor (Heffernan 2001).
Evidence
Preclinical: animal or in vitro data only
- hGH 176-191 and related C-terminal fragments caused a short-lived rise in blood glucose and a more sustained rise in insulin in rats; fragments with residues 178-191 reduced insulin sensitivity (Ng and Bornstein, 1978)
- hGH 177-191 matched the antilipogenic activity of intact hGH in rat fat pads (Wu and Ng, 1993)
- Chronic hGH 177-191 reduced weight gain and fat mass in obese ob/ob mice (Natera et al., 1994)
- Contested: the tyrosine analog AOD9604 did not raise glucose in obese mice (Heffernan et al., 2001) or in human trials (Stier et al., 2013), unlike the 1978 result for 176-191
- Human-trial status: none for hGH 176-191; human trials were run only with AOD9604
References
- Hyperglycemic action of synthetic C-terminal fragments of human growth hormone. Ng FM, Bornstein J, American Journal of Physiology, 1978
- Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone. Wu Z, Ng FM, Biochemistry and Molecular Biology International, 1993
- Reduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177-191 peptide. Natera SH, Jiang WJ, Ng FM, Biochemistry and Molecular Biology International, 1994
- Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism. Heffernan MA, Jiang WJ, Thorburn AW, Ng FM, American Journal of Physiology - Endocrinology and Metabolism, 2000
- Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats. Ng FM, Jiang WJ, Gianello R, et al., Journal of Molecular Endocrinology, 2000
- Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Heffernan MA, Thorburn AW, Fam B, et al., International Journal of Obesity and Related Metabolic Disorders, 2001
- Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Stier H, Vos E, Kenley D, Journal of Endocrinology and Metabolism, 2013
Side effects
No human safety data for hGH 176-191. In rats it produced a short-lived rise in blood glucose and insulin (Ng 1978). The related AOD9604 showed headache and GI effects at placebo-like rates in human trials (Stier 2013). Injection-site irritation and headache are commonly reported (anecdotal).
Storage
- Storage
- Refrigerate 2-8°C (36-46°F); general lyophilised-peptide guidance, no compound-specific CoA located
- Lyophilized
- 2+ years at room temp, 3+ years refrigerated
- Reconstituted
- 28-30 days refrigerated
Pharmacology
- Half-life
- Not published in any species
- Bioavailability
- Not reported. A related oral fragment (AOD9401) was active in obese mice (Heffernan 2000); no subcutaneous data
- Molecular weight
- 1799.1 Da
- Sequence
- FLRIVQCRSVEGSCGF [disulfide Cys7-Cys14]