hGH Fragment 176-191

Overview

hGH Fragment 176-191 is a synthetic peptide corresponding to the last sixteen residues of human growth hormone. It exists because of a structure–function finding: the effects of growth hormone on fat metabolism and its effects on growth turn out to be separable, and they map to different parts of the molecule. The fragment isolates the first without carrying the second.

It is studied as a research tool in adipose tissue metabolism, and is most interesting for what it does not do — a point covered in detail below.

Chemical identity

• Also known as: HGH Frag 176-191, growth hormone C-terminal fragment
• CAS number: none is registered for this compound. The number 221231-10-3, widely quoted for it in supplier material, belongs to AOD9604 — a different molecule, as set out below.
• Molecular formula: C₈₀H₁₂₇N₂₃O₂₄S₂
• Molecular weight: 1859.1 g/mol
• Classification: Growth hormone fragment, lipolytic domain
• Length: 16 residues, corresponding to positions 176–191 of the 191-residue hGH sequence
• Appearance: White lyophilised powder

The two sulfur atoms in the formula are worth noting: they are a pair of cysteines that form a disulphide bridge, closing a small loop within the fragment. That loop is part of the structure inherited from the parent hormone, and its integrity is relevant to both handling and verification — see below.

At 1,859 g/mol the molecule is past the point where a two-dimensional depiction stays readable at article width, so its composition is described rather than drawn.

Where the fragment comes from

Human growth hormone is a 191-residue protein with several distinct activities: it promotes linear growth and protein synthesis largely through IGF-1, it influences glucose handling, and it acts on adipose tissue to mobilise fat. For most of the history of GH research these were treated as inseparable consequences of one molecule acting at one receptor.

Work through the 1970s and 1980s testing synthetic fragments established that they are not. Activity relating to lipid metabolism was localised to the C-terminal region, while the growth-promoting activity requires the intact protein folded correctly enough to engage the growth hormone receptor. Residues 176–191 represent that C-terminal region isolated as a standalone peptide.

What it does not do

The defining characteristic of this fragment is its narrowness, and that is the reason it is studied at all rather than simply using growth hormone.

• It does not meaningfully engage the growth hormone receptor. Sixteen residues cannot reproduce the binding surface that the folded protein presents, so the signalling cascade that drives growth is not triggered.
• It is not reported to raise IGF-1. IGF-1 induction is downstream of hepatic GH receptor activation, which does not occur.
• It is not reported to produce the glucose effects associated with full-length GH. Growth hormone at sustained elevation antagonises insulin action; that effect is tied to receptor signalling the fragment does not initiate.

For a research design, that selectivity is the whole point: it allows adipose-tissue questions to be asked without the confounding systemic effects that full growth hormone introduces.

Mechanism, and an open question

The reported activity is on adipocytes — increased lipolysis and reduced lipogenesis in the models where it has been examined. The mechanism by which a sixteen-residue peptide with no GH receptor affinity produces those effects is, however, not fully settled.

The most-discussed hypothesis involves the beta-3 adrenergic receptor, which mediates lipolysis in adipose tissue and would be a plausible route. This has been probed directly using beta-3 adrenergic receptor knockout models, which is the right experiment — if the effect disappears in animals lacking the receptor, the receptor is required; if it persists, something else is doing the work.

The honest summary is that the mechanism remains incompletely defined, and that anyone building a study on this compound should read the knockout work directly rather than accepting the beta-3 explanation as established. It is repeated confidently across a great deal of secondary material, and the primary literature is more careful than that.

A species caveat worth taking seriously

Most of the lipolysis literature for this fragment is rodent, and there is a specific reason to be cautious about extrapolating from it.

Beta-3 adrenergic receptors are considerably more prominent in rodent adipose tissue than in human adipose tissue — a well-known difference that has repeatedly complicated obesity research, and one that has caused compounds effective in mice to disappoint elsewhere. If the fragment’s activity does depend on beta-3 signalling, findings from mouse models would be expected to overstate what happens in species where that receptor is sparse.

This is not an argument against the compound as a research tool. It is an argument for reading species carefully when interpreting the literature.

Relationship to AOD9604

AOD9604 is the closely related molecule that most of the later research on this fragment actually concerns. It is a modified version — a shorter C-terminal fragment carrying an added N-terminal tyrosine — developed to improve stability, and it progressed further into formal investigation than the unmodified fragment did.

The two are frequently conflated in secondary sources, including in supplier material. They are not the same molecule, and a study reporting on one is not automatically evidence for the other. When reading the literature, check which was actually administered.

Handling, reconstitution and storage

• Lyophilised storage: sealed, refrigerated, protected from light. Freeze for long-term storage.
• Reconstitution: add diluent slowly down the vial wall, allow to dissolve undisturbed, do not shake.
• Avoid reducing conditions. The disulphide bridge is structural. Diluents or buffers containing reducing agents — DTT, beta-mercaptoethanol, TCEP — will open it and change the peptide’s conformation. Standard bacteriostatic water is not a concern.
• After reconstitution: refrigerate, protect from light, minimise freeze–thaw cycles.
• Concentration: our peptide reconstitution calculator converts vial quantity, diluent volume and syringe size into concentration per unit.

Purity and analytical verification

Standard HPLC purity applies, quantifying how much of the material is the intended sequence rather than deletion variants from incomplete coupling.

The disulphide adds a second question that mass spectrometry can address but that is easy to overlook. A correctly folded fragment with its disulphide intact and a reduced, open-chain version of the same peptide differ by only two hydrogen atoms — a mass difference of 2 Da out of 1,859. That is detectable on a decent instrument, but only if someone is looking for it. A certificate reporting an approximate mass is not confirming disulphide integrity.

We publish third-party certificates of analysis by batch.

References

• Ng FM, Bornstein J. Hyperglycemic action of synthetic C-terminal fragments of human growth hormone. American Journal of Physiology, 1978. PMID 645904
• Heffernan M, Summers RJ, Thorburn A, et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta3-adrenergic receptor knock-out mice. Endocrinology, 2001. PMID 11713213
• Heffernan MA, Thorburn AW, Fam B, et al. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. International Journal of Obesity, 2001. PMID 11673763

Summary

hGH Fragment 176-191 is the C-terminal sixteen residues of human growth hormone, molecular formula C₈₀H₁₂₇N₂₃O₂₄S₂, molecular weight 1,859.1 g/mol, containing one structural disulphide bridge. It isolates the region of the parent hormone associated with lipid metabolism from the regions required for growth hormone receptor binding, and is reported to affect lipolysis and lipogenesis in adipocytes without raising IGF-1 or producing the glucose effects of full-length GH. Its mechanism is not fully settled — the frequently repeated beta-3 adrenergic explanation is a hypothesis that has been tested rather than an established pathway — and most of the supporting literature is rodent, in a receptor system where rodents differ from other species.

For laboratory research use only. Not for human consumption. This material is not a drug, food, or cosmetic and may not be sold or used for any purpose other than in vitro or non-human laboratory research.