Fragment 176-191 is a short peptide derived from human growth hormone (GH). It may also be regarded as an analog of the GH-releasing hormone, also known as GRF. This fragment is found at one end of the hormone’s peptide sequence, and is associated with some biochemical properties as a separate entity. At least twelve (178 to 190) of the amino acids in the sequence appear to be required for activity at the insulin receptor1. In this form, it may result in significant antagonism of this receptor, leading to insulin resistance in experimental animals1. Normally, growth hormone has a less detrimental effect on the effects of insulin, thus suggesting that glucose breakdown is promoted by the opposite end of the protein sequence2. Treatment with a peptide made of residues 177-191 of human GH may be associated with the inactivation of glycogen synthase phosphatase in rat muscle tissue, thus changing the concentration of active glycogen synthase in these cells3. Therefore, truncated forms of GH, including Fragment 177-191, may disrupt normal glucose or glycogen metabolism in vivo. Fragment 177-191 may also be responsible for reductions in the storage of fat molecules in rats, although it is not associated with the breakdown of existing fat stores5. The full, 16-amino-acid form of the fragment mimics growth-hormone releasing factor (GRF). GH- or GRF-analogs such as this may be associated with reduced adipose deposits in treated animals4.
GRF and its analogs function to increase GH release from tissues such as the pituitary gland6. Therefore, they may also have knock-on effects on the concentrations of other hormones, such as progesterone6. GRF analogs may also be more stable than the full GH protein7. Fragment 176-191 may be used in studies investigating the putative roles of GH or GRF in processes such as aging and the response to changes in the feeding patterns of test animals8. It may also be used to further the understanding of the GH-GRF-IGF regulatory axis9. GRF is also thought to target cells in other parts of the body other than the pituitary in mammals9. In fact, it may have a role in perinatal and postnatal development9. It is a member of a superfamily of peptide hormones or hormone-like molecules that include PACAP, secretin, glucagon and glucagon-like proteins9. Therefore, a stable, bioactive GRF analog is a viable research reagent.
GRF-releasing neurons are located in the hypothalamus, which implies another target for research incorporating Fragment 176-19110. These cells are still in need of study to elicit a full understanding of their function and their role in hormonal regulation.
Fragment 176-191, as the name suggests, is a peptide fragment made of the 16 residues nearest the amino-terminus of human growth hormone. Therefore, it may elicit partial GH activity, while sacrificing other aspects of this. The fragment is also a GRF analog. Therefore, it may activate cells in the anterior pituitary, affect the levels of other hormones such as IGF-1 and potentially alter glucose metabolism in some animals. GRF analogs may also be useful in models of fat metabolism and storage.
- Wade JD, Ng FM, Bornstein J, Pullin CO, Pearce JS. Effect of C-terminal chain shortening on the insulin-antagonistic activity of human growth hormone 177--191. Acta endocrinologica. 1982;101(1):10-14.
- Mondon CE, Reaven GM, Ling N, Lewis UJ, Frigeri LG. Amino-terminal peptide of growth hormone enhances insulin action in normal rats. Endocrinology. 1988;123(2):827-833.
- Macaulay SL, Armstrong JM, Bornstein J. Regulation of glycogen synthase activity in muscle by a C-terminal part sequence of human growth hormone. Archives of biochemistry and biophysics. 1983;224(1):365-371.
- Mangili A, Falutz J, Mamputu J-C, Stepanians M, Hayward B. Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat. PLoS ONE. 2015;10(10):e0140358.
- Wu Z, Ng FM. Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone. Biochemistry and molecular biology international. 1993;30(1):187-196.
- Haldar A, Prakash BS. Effects of growth hormone-releasing factor on growth hormone response, growth and feed conversion efficiency in buffalo heifers (Bubalus bubalis). Veterinary journal (London, England : 1997). 2007;174(2):384-389.
- Hu M, Tomlinson B. Growth hormone-releasing factor agonists for the treatment of HIV-associated lipodystrophy. Current opinion in investigational drugs (London, England : 2000). 2010;11(10):1143-1150.
- Sun LY, Spong A, Swindell WR, et al. Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice. eLife. 2013;2:e01098.
- Campbell RM, Scanes CG. Evolution of the growth hormone-releasing factor (GRF) family of peptides. Growth regulation. 1992;2(4):175-191.
- Shirasu K, Stumpf WE, Sar M. Evidence for direct action of estradiol on growth hormone-releasing factor (GRF) in rat hypothalamus: localization of [3H]estradiol in GRF neurons. Endocrinology. 1990;127(1):344-349.
- Nair D, Ramesh V, Li RC, Schally AV, Gozal D. Growth hormone releasing hormone (GHRH) signaling modulates intermittent hypoxia-induced oxidative stress and cognitive deficits in mouse. Journal of neurochemistry. 2013;127(4):531-540.