HGH Fragment 176-191: What the Growth Hormone Fragment Research Shows

What HGH Fragment 176-191 is

Human growth hormone is made as a 217-residue precursor. UniProt, the curated protein database, records it as entry P01241 (SOMA_HUMAN) and annotates the first 26 residues as a signal peptide, leaving the 191-residue hormone at positions 27–217. Research names such as hGH 177–191 count along that mature chain, whose last residue is 191, so residues 176 to 191 are the final sixteen: FLRIVQCRSVEGSCGF in one-letter code.

Counting backwards confirms it. The hormone ends in phenylalanine 191, and the sixteenth residue from the end, 176, is another phenylalanine. In UniProt’s own coordinates, which include the signal peptide, the stretch is numbered 202–217, and UniProt’s position 176 is a serine well inside the hormone — a trap when reading database annotations.

Two of the sixteen residues are cysteines. UniProt lists two disulfides in growth hormone, joining Cys53 to Cys165 and Cys182 to Cys189 in mature numbering. The second lies wholly inside the fragment, at its positions 7 and 14, so the synthetic peptide can carry the same disulfide-closed loop as the end of the parent hormone. Whether that bond is formed is a two-dalton question (see the mass section).

The fragment is a piece of the hormone itself, not one of the peptides that make the pituitary release growth hormone, which our growth hormone peptides research map covers.

Where the idea came from

The fragment’s history begins in the 1970s, and not where most summaries start. In 1978, F. M. Ng and J. Bornstein tested synthetic peptides matching residues 172–191, 176–191, 177–191, 178–191, 179–191 and 180–191 in normal rats, in a paper titled “Hyperglycemic action of synthetic C-terminal fragments of human growth hormone”. Four of them, 176–191 among them, “produced a short-lived rise in blood glucose and a more sustained rise in plasma insulin”; the two shortest were inert. The authors added that an active peptide needed the “correct physical configuration” as well as the right sequence. A 1987 Amgen patent, reviewing earlier studies, likewise records “a hyperglycemic effect for a peptide duplicating residues 176 through 191.”

The lipid story came fifteen years later and used a shorter peptide. In 1993, Zhao-Ming Wu and Frank Ng reported that synthetic hGH 177–191, which lacks the first phenylalanine, had “antilipogenic activity identical with that of the intact molecule”, reducing fat synthesis as growth hormone does. They found no significant lipolytic effect, measured as glycerol release from fat pads of treated rats, and concluded that growth hormone’s main effect on lipid metabolism “is at the level of lipogenesis.”

The work then moved into a company. European patent EP 1 012 189 B1, granted in 2007 to Metabolic Pharmaceuticals of Melbourne (inventors Frank Ng and Woei-Jia Jiang, priority 1997), describes native hGH 177–191 and an “elongation analogue” with an extra N-terminal tyrosine under reference numbers 9401 and 9604, the numbers the group’s papers give AOD9401 and AOD9604. It states that the native peptide “may be in cyclic disulfide form” and that in its assays “non-cyclic peptide analogues are generally inactive.”

What the animal and cell studies reported

Every lipid-metabolism study we found from this program used hGH 177–191 or its tyrosine-extended analogue; none used the native 176–191 sequence. What follows is animal, tissue and cell evidence about those two molecules, not about the native fragment, and none of it shows an effect in people.

• hGH 177–191 in rat tissue and obese rats. A 2000 Journal of Molecular Endocrinology paper from a Monash University group defined AOD9401 as the domain that “contains the amino acid residues 177-191”. It “stimulated hormone-sensitive lipase and inhibited acetyl coenzyme A carboxylase” in isolated rat adipose tissue. After chronic treatment of obese Zucker rats the authors reported lower weight gain, smaller fat cells and, unlike growth hormone, no insulin resistance or glucose intolerance.
• AOD9604 in obese rats. A 2000 Hormone Research paper reported increased lipolytic activity in adipose tissue from treated Zucker rats and, unlike chronic intact growth hormone, “no adverse effect on insulin sensitivity” by euglycemic clamp.
• AOD9604 in obese mice and cells. Heffernan and colleagues (International Journal of Obesity, 2001) reported increased fat oxidation and lipolysis in ob/ob mice given growth hormone or AOD9604, and found in receptor-bearing cells that “AOD9604 does not interact with the hGH receptor”.
• Knockout mice. In mice lacking the β3-adrenergic receptor, “the major lipolytic receptor found in fat cells”, chronic treatment “failed to produce the change in body weight” seen in normal mice, although in an acute experiment AOD9604 still raised energy expenditure and fat oxidation. The authors concluded that “the lipolytic actions of both hGH and AOD9604 are not mediated directly through the β3-AR”.

Two cautions apply. These are studies of rodents, rodent tissue and an engineered cell line, and they do not show what happens in human tissue. And the record is less tidy than summaries suggest: in 1978 hGH 177–191 briefly raised blood glucose in normal rats, while in 2000 chronic treatment of obese rats produced no glucose intolerance. The designs differ, and we found no study comparing the three sequences side by side. None of this work concerned brown fat either; our overview of what the fat-tissue research does and doesn’t show explains why that matters.

What has and hasn’t been studied in people

We found no published human study of the native 176–191 sequence. The human data that exist concern AOD9604. A 2013 paper by Heike Stier, Evert Vos and David Kenley, listing Metabolic Pharmaceuticals and Calzada as sponsors, summarized safety and tolerability data from six randomized, double-blind, placebo-controlled trials with 893 participants, two of them phase IIb studies. It reported that “AOD9604 had no effect on serum IGF-1 levels” and no efficacy outcomes such as body-weight change.

Those outcomes are the other half of the story: BioWorld reported in February 2007 that development of AOD-9604 in obesity had been terminated following phase IIb findings. No study we found took the native fragment into clinical development, and a sponsor-authored safety summary of a modified analogue is not evidence about the native peptide, or about the suitability of any research reagent for human use.

How it relates to AOD-9604

AOD9604 is Tyr-hGH 177–191: residues 177–191 with a tyrosine added at the front. Laid against the native fragment, that tyrosine sits exactly where phenylalanine 176 would be, so the two sixteen-residue peptides differ only at position 1, YLRIVQCRSVEGSCGF against FLRIVQCRSVEGSCGF. Chemically the difference is one oxygen atom, the hydroxyl that turns phenylalanine into tyrosine, worth 15.995 Da. Stier and colleagues wrote that the extra tyrosine “stabilizes the peptide”.

That single residue is why the names are easy to confuse: almost all of the animal and human work above used the tyrosine version or the shorter 177–191 peptide. The trial history and the full comparison belong to our guide on how AOD-9604 compares.

Sequence and mass at a glance

The values below are our calculations from each sequence. They assume free amino and carboxyl ends, use the 2024 abridged standard atomic weights from IUPAC’s atomic-weights commission (CIAAW) for average masses and NIST isotope masses for monoisotopic values, and subtract two hydrogen atoms for the disulfide. Our explainer on how a peptide’s mass is calculated shows the method.

The native fragment and AOD9604 sit 16.0 g/mol apart, an easy distinction for any mass measurement; the oxidized and reduced forms of the same fragment are only 2.016 apart. In electrospray spectra a peptide this size may also appear as doubly and triply charged ions, at m/z 899.940 and 600.296 for the oxidized native fragment.

What’s established and what isn’t

Checking a fragment’s identity when sourcing in Canada

For a Canadian lab, the name on a vial is the weakest identity evidence available, and a few checks do far more. Pure Peptides Canada is itself a supplier, so apply the same checks to us.

• Read the first residue. The native fragment starts with phenylalanine, FLRIVQCRSVEGSCGF. A tyrosine start, YLRIVQCRSVEGSCGF, is the AOD9604 sequence, whatever the label says.
• Compare the mass with the right row. An average mass near 1799 fits HGH Fragment 176-191 with its disulfide formed; one near 1815 fits the tyrosine analogue. Use the matching table columns for monoisotopic or [M+H]⁺ values.
• Check the disulfide state. Oxidized and reduced forms differ by 2.016 Da, and at this size the oxidized peptide’s third isotope peak is about 60% as tall as its first (our calculation), so a reduced form hides inside the isotope cluster. Judge the whole cluster; our guide to reading a mass spectrum shows how.
• Know what intact mass cannot show. Swapping two residues leaves the mass unchanged. The indexed abstract of the 1993 paper prints residues 184 and 185 as Val-Ser rather than the curated Ser-Val: the same composition and the same 1650.797 Da, but a different peptide on paper. Sequence-level evidence, such as tandem mass spectrometry, settles order.
• Ask when the documentation is silent. If a listing gives only a name, ask for the sequence and the mass its identity test was judged against. For our products, the Contact page is the route for documentation questions.

Frequently asked questions