40% OFF Everything*

SAVE NOW!

Take 35% Off!

Blogs

Disclaimer

Blogs

  • What is Fragment 176-191?

    The effects of impaired GRF release in mice (black bars) compared to healthy controls (white bars) on body length and feeding. Asterisks indicate significant difference compared to controls. From: Gautam D, Jeon J, Starost MF, et al. Neuronal M(3) muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(15):6398-6403, available through PNAS Open Access. The effects of impaired GRF release in mice (black bars) compared to healthy controls (white bars) on body length and feeding. Asterisks indicate significant difference compared to controls. From: Gautam D, Jeon J, Starost MF, et al. Neuronal M(3) muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(15):6398-6403, available through PNAS Open Access.

    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.

      

    References:

    1. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. Campbell RM, Scanes CG. Evolution of the growth hormone-releasing factor (GRF) family of peptides. Growth regulation. 1992;2(4):175-191.
    10. 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.
    11. 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.
  • What is MGF?

    MGF receptors, as detected in rabbit mesenchymal stem cells. From Xin J, Wang Y, Wang Z, Lin F. Functional and transcriptomic analysis of the regulation of osteoblasts by mechano-growth factor E peptide. Biotechnology and applied biochemistry. 2014;61(2):193-201, reproduced under the terms of the Creative Commons Attribution License MGF receptors, as detected in rabbit mesenchymal stem cells. From Xin J, Wang Y, Wang Z, Lin F. Functional and transcriptomic analysis of the regulation of osteoblasts by mechano-growth factor E peptide. Biotechnology and applied biochemistry. 2014;61(2):193-201, reproduced under the terms of the Creative Commons Attribution License

    Mechano-growth factor is derived from insulin-like growth factor IGF-11. Natural MGF is produced as a result of differential splicing of mRNA that normally expresses this hormone2. MGF may be detected in sites of tissue damage3. For example, it may induce accelerated growth in injured skeletal muscle tissue4. Therefore, it is regarded as a response to mechanical stress on tissues. However, chemical and thermal stress may also be associated in the expression of MGF5. It may be released in response to the presence of myofibrillar proteins, and may increase the concentrations of cyclic AMP in cultured muscle cells2. The inhibition of adenylyl cyclase was also associated with reduced MGF synthesis, suggesting that this enzyme is involved in MGF regulation5. A group of researchers also reported that the administration of hydrocortisone abolished MGF expression in cultured muscle cells and tissues2. Other forms of mechanical stress may also be associated with MGF expression4. Some researchers assert that treatment with MGF results in improved muscle tissue re-modeling following injury1. Therefore, MGF may be applied in studies and models of tissue repair and regeneration6. The molecular weight of MGF is nearly 2.9kDa, and it is available as a laboratory-grade compoundi. It has a receptor, which is found in locations such as the surfaces of some stem cell types7.

    The mechanism by which MGF induces hypertrophy in stressed tissues is not as yet clear1. A 2014 study using murine muscle tissue and cells in culture found that it did not affect a number of markers of differentiation1. Interestingly, the peptide may be associated with differentiation in other tissue types. Rabbit stem cells incubated with up to 75ng/ml MGF exhibited differentiation into bone cells, which was associated with protein kinase B signaling7. However, no significant differences were reported in this study. Other groups have claimed that protein kinase B and its activation is required for similar effects in cardiac cells1. A further study using rat bone progenitor cells indicated that MGF acts to enhance the proliferation, rather than the differentiation, of these cells6. More chronic treatment with MGF, however, may promote differentiation at a later stage of bone tissue development (or regeneration)6.

    Hypertrophy and abnormal heart function are detrimental side-effects of myocardial infarction8. Mice that underwent experimental infarctions received chronic MGF treatment for ten weeks8. This resulted in significant improvements in cardiac function, but did not affect hypertrophy, compared to control animals8. It would stand to reason that MGF would be present in the growth plates (sites in bone along which cells proliferate and are distributed to increase the length of said bone) of young animals4. A recent study using infant pigs detected MGF mRNA in these sites4. The peptide, however, does not appear to function to affect proliferation in the growth plates4.

    Mechano-growth factor is a truncated form of IGF-1 which may be expressed in vivo in response to a variety of cellular stress. Some studies infer that it functions to enhance the proliferation of cells in response to damage and to induce hypertrophy in growing tissues.

    References:

    1. Fornaro M, Hinken AC, Needle S, et al. Mechano-growth factor peptide, the COOH terminus of unprocessed insulin-like growth factor 1, has no apparent effect on myoblasts or primary muscle stem cells. American journal of physiology. Endocrinology and metabolism. 2014;306(2):E150-156.
    2. Kravchenko IV, Furalyov VA, Popov VO. Stimulation of mechano-growth factor expression by myofibrillar proteins in murine myoblasts and myotubes. Molecular and cellular biochemistry. 2012;363(1-2):347-355.
    3. Vassilakos G, Philippou A, Tsakiroglou P, Koutsilieris M. Biological activity of the e domain of the IGF-1Ec as addressed by synthetic peptides. Hormones (Athens, Greece). 2014;13(2):182-196.
    4. Schlegel W, Raimann A, Halbauer D, et al. Insulin-like growth factor I (IGF-1) Ec/Mechano Growth factor--a splice variant of IGF-1 within the growth plate. PloS one. 2013;8(10):e76133.
    5. Kravchenko IV, Furalyov VA, Popov VO. Hyperthermia and acidification stimulate mechano-growth factor synthesis in murine myoblasts and myotubes. Biochemical and biophysical research communications. 2008;375(2):271-274.
    6. Xin J, Wang Y, Wang Z, Lin F. Functional and transcriptomic analysis of the regulation of osteoblasts by mechano-growth factor E peptide. Biotechnology and applied biochemistry. 2014;61(2):193-201.
    7. Tong Y, Feng W, Wu Y, Lv H, Jia Y, Jiang D. Mechano-growth factor accelerates the proliferation and osteogenic differentiation of rabbit mesenchymal stem cells through the PI3K/AKT pathway. BMC biochemistry. 2015;16(1):1.
    8. Shioura K, Pena J, Goldspink P. Administration of a Synthetic Peptide Derived from the E-domain Region of Mechano-Growth Factor Delays Decompensation Following Myocardial Infarction. International journal of cardiovascular research. 2014;3(3):1000169.
    9. MGF Product Page. Blue Sky Peptide. 2016
  • Know about: Thymosin Beta 4 (TB500)

    - Cells containing thymosin beta-4 (Tβ4) co-localize to alpha-smooth muscle actin (alphaSMA), indicating that the protein is active in the presence of fibrosis (induced by experimental chronic liver damage generated by treatment with CCI4). From: Kim J, Wang S, Hyun J, et al. Hepatic Stellate Cells Express Thymosin Beta 4 in Chronically Damaged Liver. PloS one. 2015;10(3):e0122758, reproduced under the terms of the Creative Commons Attribution License - Cells containing thymosin beta-4 (Tβ4) co-localize to alpha-smooth muscle actin (alphaSMA), indicating that the protein is active in the presence of fibrosis (induced by experimental chronic liver damage generated by treatment with CCI4). From: Kim J, Wang S, Hyun J, et al. Hepatic Stellate Cells Express Thymosin Beta 4 in Chronically Damaged Liver. PloS one. 2015;10(3):e0122758, reproduced under the terms of the Creative Commons Attribution License

    Thymosin beta-4 is a protein originally discovered as an isolate from the mammalian thymus gland1. It is one of a family of thymosins, which are low-weight acidic molecules that can act as cytopoietics. This means that they can control the movement and/or differentiation of cells by neutralizing the ability of individual actin proteins (or monomers) to polymerize into filaments2. On the other hand, thymosins also aggregate the actin monomers, thus allowing or preventing the formation of subsequent filaments2. At a certain scale, this may promote or prevent the differentiation of a cell such as a pluripotent stem cell into another, such as an osteocyte or a neural cell. Therefore, molecules such as thymosins (of which thymosin beta-4 is the most common in mammals3) may play a significant role in postnatal development or the regeneration of some tissues. The influence of thymosin beta-4 over actin may also control cellular migration and angiogenesis4. It follows, therefore, that the protein also has potential as an agent of wound repair. Thymosin beta-4 is available as a synthetic, laboratory-grade peptide known as TB500­i. Its molecular weight is just over 4.9kDa, and it is supplied as a white solid i.

    TB500 also has anti-inflammatory properties. It has demonstrated the ability to attenuate the release of NO and prostaglandin E4 in cellular models of reactive oxygen species (ROS) exposure5. However, it may also upregulate pro-inflammatory cytokines such as TNFalpha and several interleukins (e.g. IL-6 and -8) in periodontal cells5. As these molecules are also osteoclastogenic5, it implies an additional role for TB500 in the regulation of bone formation. The peptide also inhibited the activation of NFkappaB in murine macrophages in this study5. TB500 also concerns the release of acSDKP, an anti-inflammatory peptide fragment. This fragment is in fact a breakdown product of TB500, but this metabolism is regulated by a number of interesting factors6. The co-incubation of TB500 with homogenated rodent kidney tissue resulted in a significant increase in the release of acSDKP7. This is controlled by a complex regulatory mechanism which involves peptidases that only cleave molecules of specific fragments, necessitating the hydrolysis of TB500 by meprin-alpha before acSDKP may be cleaved from it7. TB500 may also be of interest to researchers studying the fibrosis of various organs8. One group has recently published results that indicate significant decreases of inflammation in a mouse model of pulmonary fibrosis9. acSDKP has been shown to decrease renal fibrosis in mice, in that treatment with the fragment resulted in the reduced deposition of fibronectin and collagen (i.e. major components of scar tissue) and the reduced migration of macrophages and myofibroblasts to a site of damage6. The up-regulation of thymosin beta-4 is also associated with the activation of hepatic stellate cells, which appear to co-localize to alpha-smooth muscle actin (a marker of chronic liver damage as observed in mouse models of the same)10.

    In general, TB500 is a peptide involved in complex regulatory and developmental processes in vivo. It appears to be a viable component of the control of tissue regeneration, cell differentiation and inflammation. Therefore, B500 may be applied to models of disorders such as abnormal fibrosis, osteolytic inflammation (e.g. rheumatoid arthritis) and various states of postnatal development.

     

    References:

    1. Goldstein AL, Slater FD, White A. Preparation, assay, and partial purification of a thymic lymphocytopoietic factor (thymosin). Proceedings of the National Academy of Sciences of the United States of America. 1966;56(3):1010-1017.
    2. Huff T, Muller CS, Otto AM, Netzker R, Hannappel E. beta-Thymosins, small acidic peptides with multiple functions. The international journal of biochemistry & cell biology. 2001;33(3):205-220.
    3. Cha HJ, Philp D, Lee SH, Moon HS, Kleinman HK, Nakamura T. Over-expression of thymosin beta 4 promotes abnormal tooth development and stimulation of hair growth. The International journal of developmental biology. 2010;54(1):135-140.
    4. Philp D, Goldstein AL, Kleinman HK. Thymosin beta4 promotes angiogenesis, wound healing, and hair follicle development. Mechanisms of ageing and development. 2004;125(2):113-115.
    5. Lee S-I, Yi J-K, Bae W-J, Lee S, Cha H-J, Kim E-C. Thymosin Beta-4 Suppresses Osteoclastic Differentiation and Inflammatory Responses in Human Periodontal Ligament Cells. PloS one. 2016;11(1):e0146708.
    6. Zuo Y, Chun B, Potthoff SA, et al. Thymosin beta4 and its degradation product, Ac-SDKP, are novel reparative factors in renal fibrosis. Kidney international. 2013;84(6):1166-1175.
    7. Kumar N, Nakagawa P, Janic B, et al. The anti-inflammatory peptide Ac-SDKP is released from thymosin beta4 by renal meprin alpha and prolyl oligopeptidase. American journal of physiology. Renal physiology. 2016:ajprenal.00562.02015.
    8. Peng H, Xu J, Yang XP, et al. Thymosin-beta4 prevents cardiac rupture and improves cardiac function in mice with myocardial infarction. American journal of physiology. Heart and circulatory physiology. 2014;307(5):H741-751.
    9. Conte E, Genovese T, Gili E, et al. Protective effects of thymosin beta4 in a mouse model of lung fibrosis. Annals of the New York Academy of Sciences. 2012;1269:69-73.
    10. Kim J, Wang S, Hyun J, et al. Hepatic Stellate Cells Express Thymosin Beta 4 in Chronically Damaged Liver. PloS one. 2015;10(3):e0122758.
    11. TB500 Product Page. Blue Sky Peptide. 2016
  • What is the difference between a peptide and a protein?

    Tesamorelin, a 44-amino acid peptide that is an analog of full GRP. By Vaccinationist - Egrifta (tesamorelin for injection) for Subcutaneous Use. U.S. Full Prescribing Information. Page 4, Public Domain, https://commons.wikimedia.org/w/index.php?curid=48094028 Tesamorelin, a 44-amino acid peptide that is an analog of full GRP. By Vaccinationist - Egrifta (tesamorelin for injection) for Subcutaneous Use. U.S. Full Prescribing Information. Page 4, Public Domain, https://commons.wikimedia.org/w/index.php?curid=48094028

    Peptides and proteins are often very discrete terms; however, they refer to biological molecules that often overlap in terms of function and other factors. A peptide is a ‘chain’ of amino acids that is expressed as a result of mRNA translation. This is often thought of as the ‘primary’ dimension of protein structure. Many scientists throughout history may not have thought of a single chain as a complete protein. This is due to the theories of protein structure as composed of multiple chains. In addition, even individual chains may attain additional structural complexity. This complexity is conferred by interactions between the side-chains of the amino acids within the chain. These mainly give rise to alpha-helices or beta-pleated sheets. Shapes such as these are regarded as the secondary degree of protein structures. Complicated chains may then proceed to interact (i.e. ‘interlock’ or form interfaces) with others expressed from the same gene to form certain structures. Common examples of these are known as globular structures and zinc-finger structures. This is known as tertiary protein structures, and also as proteins domains (specific subunits or characteristics). One or more domains may then form interactions or bonds (e.g. sulphide bridges) to form proteins with a quaternary structure.

    This is the classical view of proteins, which gives rise to their perception as complex molecules that may have a higher weight and three-dimensional size. There are a number of other properties that are also associated with proteins. An example of these is the structure-to-function relationship; essentially how a protein’s structure, once it has been produced as above, defines its role in a living system. However, some peptides present arguments that may dispute these classical characteristics.

    At the outset of biological research, it may have been thought that proteins required chains with very large numbers of amino acids to carry out the roles increasingly associated with this class of molecule. This is true for some proteins, which require many specific domains in a definitive conformation to interact with their targets. On the other hand, some peptides with relatively short chains may elicit at least some of the functions of larger proteins from which they have been derived1. For example, a twelve-residue peptide fragment may bind to the receptor of the full insulin protein2. Therefore, a peptide may have some protein-like functions. Similarly, IGF-1 is a protein with several domains that has various regulatory functions in the body. Mechano-growth factor (MGF) is a peptide that is an equivalent to just one domain (the E-domain) of IGF-13. Despite its reduced complexity, however, it is active at receptors of its own and is specifically expressed from the IGF1 gene in response to mechanical damage to muscle tissue3.

    In other words, a typical defining feature of proteins is that it is biologically active, i.e. that it binds a receptor or another protein to affect signaling within a cell. This may require a particularly-shaped protein with at least one domain – i.e. a complex and specific 3D structure. However, GRF is a relatively short peptide that can bind a receptor to enhance growth hormone (GH) release1. In addition, there are even smaller peptides - only six residues long - that may be comparably effective, and are thus known as synthetic GH secretagogues (GHSs)4. This is due to a certain motif, (or specific sequence of amino acids) contained within the six-amino-acid chain, that interacts effectively with the GHS receptor5. Small peptides, containing relevant motifs, also have other advantages over proteins such as increased absorption due to their small size. In general, all proteins may be considered peptide chains, but not all functional peptides need be proteins.
    References:

    1. Ionescu M, Frohman LA. Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long-Acting GH-Releasing Hormone Analog. The Journal of Clinical Endocrinology & Metabolism. 2006;91(12):4792-4797.
    2. 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.
    3. Shioura K, Pena J, Goldspink P. Administration of a Synthetic Peptide Derived from the E-domain Region of Mechano-Growth Factor Delays Decompensation Following Myocardial Infarction. International journal of cardiovascular research. 2014;3(3):1000169.
    4. Cheng K, Chan WW, Barreto A, Jr., Convey EM, Smith RG. The synergistic effects of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 on growth hormone (GH)-releasing factor-stimulated GH release and intracellular adenosine 3',5'-monophosphate accumulation in rat primary pituitary cell culture. Endocrinology. 1989;124(6):2791-2798.
    5. Ferro P, Krotov G, Zvereva I, Rodchenkov G, Segura J. Structure-activity relationship for peptidic growth hormone secretagogues. Drug testing and analysis. 2016.
  • What is IGF-1 LR3?

    Effects of IGF-1 LR3 on the estradiol production in porcine granulosa cells (‘b’ indicates a significant difference). From Brankin V, Mitchell MR, Webb B, Hunter MG. Paracrine effects of oocyte secreted factors and stem cell factor on porcine granulosa and theca cells in vitro. Reproductive biology and endocrinology : RB&E. 2003;1:55, reproduced under the terms of the Creative Commons Attribution License Effects of IGF-1 LR3 on the estradiol production in porcine granulosa cells (‘b’ indicates a significant difference). From Brankin V, Mitchell MR, Webb B, Hunter MG. Paracrine effects of oocyte secreted factors and stem cell factor on porcine granulosa and theca cells in vitro. Reproductive biology and endocrinology : RB&E. 2003;1:55, reproduced under the terms of the Creative Commons Attribution License

    Insulin-like growth factor-1 (IGF-1) is a protein with a role in growth hormone- (GH) induced signaling, development and other functions1. For example, the IGF-1 levels of some mammalian species change in response to feeding and changes in the amounts of food-generated energy2. IGF-1 is regarded as a peptide hormone, an endocrine factor and a paracrine factor, depending on the part of the body in which it is active3. It is available as a laboratory-grade compound known as IGF-1 LR3. This synthetic analog of IGF-1 has an arginine residue in place of the normal glutamic acid in the third position along its sequence. IGF-1 LR3 also has an elongated amino-terminus, to give a protein of 83 amino acids as opposed to the 70 found in the natural or endogenous molecule. These variations impair the ability of IGF-binding proteins (IGFBP) in vivo or in vitro1. IGFBPs are involved in the regulation of IGF-1 and its activity at the IGF receptor. Therefore, IGF-1 LR3 may be more potent when administered in comparison to normal IGF-11. On the other hand, it may also have greater clearance from the blood due to the lack of binding. The affinity of IGF-1 for the IGF receptor is poor compared to that of IGFBPs for IGF-11. Therefore, binding proteins can exert considerable negative regulation on IGF receptor activation. (Conversely, some IGFBP subtypes promote IGF-1 activity, depending on a number of factors including their phosphorylation status1.) Modified IGF can have a 100-fold (or more) reduction in affinity for IGFBPs compared to the original molecule1. IGF-1 LR3 may have a potency that is approximately two-fold greater than that of IGF-1, as evidenced by a study using rats4. IGF-1 has a molecular weight of about 7kDa; IGF-1 LR3 may be a little larger than this4.

    Treatment with IGF-1 LR3 is associated with significant increases in sodium ion flux across the gut epithelium of sheep2. This indicates a role for IGF-1 in the essential nerve cell activity, motility and pH regulation in the digestive tract. IGF-1 LR3 has also been used to assess the role of IGF-1 in follicle development in mammals. Both IGF-1 LR3 and recombinant human IGF-1 were associated with dose-dependent increases in the size and estradiol release of cultured bovine follicles5. However, higher doses of IGF-1 resulted in reduced oocyte numbers, indicating that follicular development depends on the tight regulation of IGF-1 activity5. This may be supported by the detection of IGFBP2 and of IGFBP3 mRNA in the cultured follicles5. IGF-1 LR3 may also be used to assess the overexpression of IGF receptors often observed in tumor cells6. It is associated with cyclin D1 activity, a marker of cell cycle activity, mediated by the IGF receptor in these cells6. The function of this is to enhance the proliferation, survival and invasive migration of tumors6. IGF-1 LR3 may also be applied to studies assessing novel antagonists of this receptor intended to prevent this. Another function of IGF-1 LR3 is to assess the expression patterns of IGFBPs in various tissues. For example, a recent study found that these are not regulated by the presence of IGF in murine skeletal muscle7.

    References:

    1. Mohan S, Baylink DJ. IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms. The Journal of endocrinology. 2002;175(1):19-31.
    2. Shen Z, Martens H, Schweigel-Rontgen M. Na+ transport across rumen epithelium of hay-fed sheep is acutely stimulated by the peptide IGF-1 in vitro. Experimental physiology. 2012;97(4):497-505.
    3. Brankin V, Mitchell MR, Webb B, Hunter MG. Paracrine effects of oocyte secreted factors and stem cell factor on porcine granulosa and theca cells in vitro. Reproductive biology and endocrinology : RB&E. 2003;1:55.
    4. Tomas FM, Lemmey AB, Read LC, Ballard FJ. Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection. The Journal of endocrinology. 1996;150(1):77-84.
    5. Thomas FH, Campbell BK, Armstrong DG, Telfer EE. Effects of IGF-I bioavailability on bovine preantral follicular development in vitro. Reproduction (Cambridge, England). 2007;133(6):1121-1128.
    6. Haluska P, Carboni JM, Loegering DA, et al. In vitro and in vivo antitumor effects of the dual insulin-like growth factor-I/insulin receptor inhibitor, BMS-554417. Cancer research. 2006;66(1):362-371.
    7. Oliver WT, Rosenberger J, Lopez R, Gomez A, Cummings KK, Fiorotto ML. The local expression and abundance of insulin-like growth factor (IGF) binding proteins in skeletal muscle are regulated by age and gender but not local IGF-I in vivo. Endocrinology. 2005;146(12):5455-5462.
  • How Ipamorelin Works

    The effect of ipamorelin treatment on diabetic (D/IPA) and healthy (C/IPA) mice compared to saline-treated controls. From: Johansen PB, Segev Y, Landau D, Phillip M, Flyvbjerg A. Growth hormone (GH) hypersecretion and GH receptor resistance in streptozotocin diabetic mice in response to a GH secretagogue. Experimental diabesity research. 2003;4(2):73-81, reproduced under the terms of the Creative Commons Attribution License The effect of ipamorelin treatment on diabetic (D/IPA) and healthy (C/IPA) mice compared to saline-treated controls. From: Johansen PB, Segev Y, Landau D, Phillip M, Flyvbjerg A. Growth hormone (GH) hypersecretion and GH receptor resistance in streptozotocin diabetic mice in response to a GH secretagogue. Experimental diabesity research. 2003;4(2):73-81, reproduced under the terms of the Creative Commons Attribution License

    Ipamorelin is a hexapeptide (or six-amino-acid) that was developed to mimic ghrelin and its in vivo properties. Until other similar molecules, such as GHRP-1, -2 and -6, ipamorelin contains synthetic amino acids1. The main function of ipamorelin is to increase the production of growth hormone (GH) from cells that express the GHS-R receptor (also known as the ghrelin receptor). It may also increase IGF-1 levels in healthy animals2. However, other similar molecules, such as those listed above, may be associated with significant increases in ACTH and cortisol, whereas ipamorelin is not1. Nevertheless, ipamorelin may affect growth and development in a manner similar to GH and other ghrelin mimetics (i.e. the GHRPs). Female rats were treated with comparable doses of GH, GHRP and ipamorelin for eight-weeks. This resulted in similar and significant increases in body weight for all three treatments3. Therefore, ipamorelin may be used as a comparative reagent in the assessment of GHS-R activation and GH release in novel or less-studied species4. It may also be applied to studies investigating the effects of GH release on subsequent GH expression in these species. For example, ipamorelin was recently incorporated into a study indicating that GH release does not depend on or is influenced by GH mRNA transcription in the black sea bream4. (The expression of GH and GHS-R activation act synergistically, or as a positive feedback loop, in some mammalian species4. This can also be confirmed through the use of ipamorelin.) Therefore, ipamorelin may be active at many cell types that release GH in vivo. These include, but are not limited to, pituitary, cardiac and liver cells.

    GH is also associated with a role in normal bone growth and structure. Therefore, ipamorelin may also have a role in bone formation. A study compared bone mass (measured as bone mineral density) in rats treated with 0.5 mg/kg ipamorelin, 0.5 mg/kg GHRP-6, 3.5 mg/kg GH or a placebo every day for eight weeks. Ipamorelin was associated with significant increases in post mortem bone mineral content scans, although to a lesser extent than GH or GHRP-6, compared to placebo3. However, the total weights of vertebrae from ipamorelin-treated rats were significantly greater than those from rats in the placebo group, and were comparable to those taken from GH- and ghrp-6-treated rats3. Ipamorelin also appears to have beneficial effect in animal models of diabetes, as does ghrelin5. The peptide has demonstrated the ability to increase insulin production in the pancreatic tissue of diabetic and non-diabetic rats6. Unlike ghrelin, however, ipamorelin appears to elicit these effects via adrenergic receptors and through calcium channel activation6. Treatment with ipamorelin also results in significant increases in GH concentrations in diabetic mice when compared to non-diabetic mice2. This indicates GH resistance, an indicator of type 1 diabetes. Normal mice treated with ipamorelin exhibited significant increases in hepatic IGF-1 compared to identical controls, whereas diabetic, treated mice showed significantly reduced levels of this protein compared to their healthy counterparts2. These results demonstrate how ipamorelin can be used to highlight the abnormal hepatic response to GH in this model of diabetes.

    References:

    1. Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. European journal of endocrinology / European Federation of Endocrine Societies. 1998;139(5):552-561.
    2. Johansen PB, Segev Y, Landau D, Phillip M, Flyvbjerg A. Growth hormone (GH) hypersecretion and GH receptor resistance in streptozotocin diabetic mice in response to a GH secretagogue. Experimental diabesity research. 2003;4(2):73-81.
    3. Svensson J, Lall S, Dickson SL, et al. The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. The Journal of endocrinology. 2000;165(3):569-577.
    4. Chan CB, Fung CK, Fung W, Tse MC, Cheng CH. Stimulation of growth hormone secretion from seabream pituitary cells in primary culture by growth hormone secretagogues is independent of growth hormone transcription. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. 2004;139(1-3):77-85.
    5. Adeghate E, Ponery AS. Ghrelin stimulates insulin secretion from the pancreas of normal and diabetic rats. J Neuroendocrinol. 2002;14(7):555-560.
    6. Adeghate E, Ponery AS. Mechanism of ipamorelin-evoked insulin release from the pancreas of normal and diabetic rats. Neuro Endocrinol Lett. 2004;25(6):403-406.
  • GHRP-6 and its uses

    The effects of GHRP-6 on cell differentiation to myocytes (i.e. myogenesis). From: Lim CJ, Jeon JE, Jeong SK, et al. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I. BMB Reports. 2015;48(9):501-506, reproduced under the terms of the Creative Commons Attribution License The effects of GHRP-6 on cell differentiation to myocytes (i.e. myogenesis). From: Lim CJ, Jeon JE, Jeong SK, et al. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I. BMB Reports. 2015;48(9):501-506, reproduced under the terms of the Creative Commons Attribution License

    Growth hormone releasing peptides (GHRPs) are short molecules developed to mimic the growth hormone secretagogue (GHS, or ghrelin) as the name suggests. Interest in these small sequences began in the early 1980s. At this time, GHRP-6 was regarded as the most potent of these compounds1. GHRP-6 is active at the GHS receptor (GHS-R) and may therefore activate or regulate a number of different pathways in animal systems. Ghrelin and/or GH may mediate effects on metabolism, appetite, cardiac function and/or protection and cell survival. Therefore, GHRP-6 may be a useful reagent in animal models of various conditions, ranging from ischemia to obesity.

    GHRP-6 may be administered by injection, topically or orally. However, there are other ghrelin mimetics that may be more effective when administered by the latter route1. Intranasal delivery systems for this peptide have also been proposed2. GHRP-6 has limited stability and availability as a topical treatment, unless modified or conjugated to another small molecule3. One group recently reported improvements in these properties through the conjugation of GHRP-6 to biotin, and that this formulation elicited significantly increased collagen synthesis in cultured skin cells3. The same group then applied this compound to cultured myoblasts, and reported that this treatment resulted in significant increases in their differentiation to myocytes when compared to control cells3. This was thought to be associated with increased collagen-I synthesis3. Treatment with GHRP-6-biotin was also associated with significant increases in intracellular ATP and lactate compared to controls, indicating that treated cells used more energy than non-treated cells3. These findings may align with others that indicate GH may regulate the expression of various genes involved in myoblast differentiation through IGF signaling4.

    Many researchers have concluded that GHS and its mimetics also act to prevent apoptosis in a number of cell types5. Apoptosis in pituitary cells, as well as hypothalamic and cerebellar astrocytes, has been observed as a side-effect of diabetes5. This condition may also result in a decrease in GH expression5. Therefore, GHRP-6 may be used in relevant studies to assess the effects of GH or ghrelin on both diabetes and diabetes-induced cell death. A 2011 study compared a daily regimen of either GHRP-6, (150μg/kg) this dose of the same combined with approximately 8IU insulin, insulin alone or a placebo on apoptosis in rats with experimentally-induced diabetes5. Rats with this condition exhibited significantly more apoptosis in the cell types listed above compared to control animals. As individual treatments, GHRP-6 and insulin did not significantly affect cell death after eight weeks. However, the ‘combined’ treatment was associated with significant decreases in apoptosis and in the concentrations of glial fibrillary acidic protein, a marker of nerve cell damage5. GHRP-6 may also enhance the survival of heart muscle cells following experimentally-induced cardiac disease6. A single treatment of 400μg/kg in an animal model of acute myocardial infarction was associated with significant reductions in cardiac injuries and oxidative stress compared to controls6. GHRP-6 may also be used to assess the putative roles of GH in other processes, most notably aging and hormonal dysregulation7.

    References:

    1. DeVita RJ. Small molecule mimetics of GHRP-6. Expert opinion on investigational drugs. 1997;6(12):1839-1843.
    2. Pontiroli AE. Peptide hormones: Review of current and emerging uses by nasal delivery. Advanced drug delivery reviews. 1998;29(1-2):81-87.
    3. Lim CJ, Jeon JE, Jeong SK, et al. Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I. BMB Reports. 2015;48(9):501-506.
    4. Florini JR, Ewton DZ, Coolican SA. Growth hormone and the insulin-like growth factor system in myogenesis. Endocrine reviews. 1996;17(5):481-517.
    5. Granado M, Garcia-Caceres C, Tuda M, Frago LM, Chowen JA, Argente J. Insulin and growth hormone-releasing peptide-6 (GHRP-6) have differential beneficial effects on cell turnover in the pituitary, hypothalamus and cerebellum of streptozotocin (STZ)-induced diabetic rats. Molecular and cellular endocrinology. 2011;337(1-2):101-113.
    6. Berlanga J, Cibrian D, Guevara L, et al. Growth-hormone-releasing peptide 6 (GHRP6) prevents oxidant cytotoxicity and reduces myocardial necrosis in a model of acute myocardial infarction. Clinical science (London, England : 1979). 2007;112(4):241-250.
    7. Zouboulis CC, Makrantonaki E. Hormonal therapy of intrinsic aging. Rejuvenation research. 2012;15(3):302-312.
  • What is CJC-1295 No DAC?

    This image shows the difference in size and length between a mouse carrying a mutation that impairs the release of GRF (Br-M3-KO, right) in the brain and an identical healthy control (left). From: Gautam D, Jeon J, Starost MF, et al. Neuronal M(3) muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(15):6398-6403, available through PNAS Open Access This image shows the difference in size and length between a mouse carrying a mutation that impairs the release of GRF (Br-M3-KO, right) in the brain and an identical healthy control (left). From: Gautam D, Jeon J, Starost MF, et al. Neuronal M(3) muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(15):6398-6403, available through PNAS Open Access

    What is CJC-1295 No DAC?

    CJC-1295 is an isoform of the growth hormone releasing hormone (GHRH), also popularly known as GH-releasing factor or GRF. This protein is produced in the hypothalamus of many animals, and targets receptors on somatotrophic cells in the pituitary when released1. It may be applied as a treatment for growth disorders, or with the intention of tissue mass enhancement; in which case it is bound to a drug-affinity complex (or DAC) which is intended to control its release over time when administered. However, the peptide as referred to in the title above is CJC-1295 NO-DAC, or modified GRF without DACi. Therefore, it may also be referred to as modGRF, or the first 29 amino acids that comprise the original GRF moleculei. Native GRF, on the other hand, may have as many as 44 amino acids2, although residues 1-29 have been shown to exert all the biological properties associated with this protein3. modGRF weighs just under 3.4kDa, is synthetically produced and is suitable for research use onlyi. The main function of modGRF is to enhance the release of GH, as mentioned above. Therefore, it may be useful in studies of growth and development. Some studies indicate that modGRF has pharmacokinetic and pharmacokinetic properties that are superior to endogenous GHRH4. It may have increased activity in vivo and a greater half-life compared to un-modified GRF4.

    Human GRF (or GRF1-44) may be regarded as a ‘reference’ GRF, and was used as a template for many GRF analogs. However, its modification in respect to the isoforms of other species may confer benefits. For example, substituting the first two amino acids for those of the murine sequence reportedly inhibits metabolism by a peptidase, thus improving stability in cell culture studies2. Additionally, replacing the eighth residue in the human sequence (asparagine) with serine, (as in the rat sequence) threonine (mouse) or glutamine (synthetic) results in further stability and enhanced conformity to one peptide conformation2. Substituting alanine for the original glycine at the fifteenth residue is thought to increase receptor binding2. Another measure of GRF optimization is truncation, as outlined above. This may make improve many factors of potency for this molecule2.

    GRF has other targets beside GH. The administration of CJC-1295 has resulted in significant increases in the release of IGF-13. Endogenous GRF, GH and IGF-1 form a regulatory ‘axis’ that may also control pro-inflammatory mechanisms when activated5. The peptide has also demonstrated the ability to reduce growth deficits in a mouse model of GHRH knockout. Knockout mice treated with 2µg CJC-1295 daily for five weeks achieved significantly increased total body weight and length compared to placebo-treated knockout animals6. The body weight and length of knockout mice treated daily with CJC-1295 was also comparable to ‘normal’ untreated mice6. Therefore, modGRF may also have profound effects on growth in experimental animals. It may also be used to assess the abnormal response to GRF that has been observed in rodent models of obesity7. Rats with genetically-induced obesity have exhibited significant decreases in GH release following treatment with GRF in a time-dependent manner (i.e. at eight weeks following birth compared to six weeks)7. In summary, modGRF is a useful lab-grade peptide that may be applied to studies of growth, development and metabolic disorders.

    References:

    1. Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ. Activation of the GH/IGF-1 axis by CJC-1295, a long acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2009;19(6):471-477.
    2. Campbell RM, Stricker P, Miller R, et al. Enhanced stability and potency of novel growth hormone-releasing factor (GRF) analogues derived from rodent and human GRF sequences. Peptides. 1994;15(3):489-495.
    3. Ionescu M, Frohman LA. Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long-Acting GH-Releasing Hormone Analog. The Journal of Clinical Endocrinology & Metabolism. 2006;91(12):4792-4797.
    4. Jette L, Leger R, Thibaudeau K, et al. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005;146(7):3052-3058.
    5. Qin YJ, Chan SO, Chong KKL, et al. Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation. Proceedings of the National Academy of Sciences of the United States of America. 2014;111(51):18303-18308.
    6. Alba M, Fintini D, Sagazio A, et al. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. American journal of physiology. Endocrinology and metabolism. 2006;291(6):E1290-1294.
    7. Renier G, Gaudreau P, Deslauriers N, Petitclerc D, Brazeau P. Dynamic of the GRF-induced GH response in genetically obese Zucker rats: influence of central and peripheral factors. Regulatory peptides. 1990;28(1):95-106.
    1. CJC-1295 NO-DAC Product Page. Bluesky Peptides. 2016
  • Know About: Follistatin 344

    - Follistatin, by Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute via Wikimedia Commons - Follistatin, by Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute via Wikimedia Commons

    Follistatin 344 (or FS-344) acts as a precursor to the protein follistatin when administered to animals as a laboratory-grade peptide. Mature follistatin regulates the release of follicle-stimulating hormone (FSH) through the inhibition of activin1. Naturally, activin (also known as activin-A) is classically viewed as an FSH-level promoter, although it may have other roles in accordance to the part of the body in which it is present. Therefore, FS-344 may be present in any tissue that also contains activin (according to some studies on rats). These include skeletal muscle, several vital organs, the thymus and part of the cerebral cortex, although the majority of follistatin molecules may be found in the gonads and anterior pituitary2. Follistatin also has other targets in vivo, the best-studied of which are myostatin and growth differentiation factor-11 (GDF-11)1. This may be due to the close homogeneity in structure between activin and these additional proteins3. Myostatin and GDF-11 were also perceived as similar in function at one time, although more up-to-date research indicates that they have wildly different roles in mammalian systems3. Myostatin is associated with muscle development after birth, whereas GDF-11 has more diverse functions in development3. This suggests a diverse range of future applications for follistatin and for derivatives such as FS-344.

    There are a number of applications for FS-344 in the laboratory and in animal studies. These may mostly concern experiments on the roles of activin in various tissues, due to the influence of follistatin on this protein. FS-344 is composed of all the amino acids that can comprise the protein, whereas species-specific isoforms are spliced or further processed into slightly smaller variants (e.g. FS-315)4. The presence of FS-344 mRNA was originally confirmed in porcine studies5. It has also been found in rats, and stood out at the time as the most abundant messenger RNA associated with follistatin precursors (of which there are indeed others, e.g. FS-317) in this animal2. FS-344 also distinguishes itself through a novel 27-amino acid tail at the C-terminus, which other smaller follistatin precursors lack5. Follistatin derivatives have also recently attracted attention as research agents in murine models of muscle growth and development1,6. This is due to the inhibitory effects of the protein on myostatin, which has a role in the negative regulation of cardiac and skeletal muscle mass3.

    Some groups have also reported results suggesting roles for follistatin and/or its derivatives in inflammatory processes, scar tissue formation, hair growth and tissue re-modeling4,7,8. The anti-inflammatory effects of follistatin are most likely to be due to its binding of activin, which has been shown to be released in response to animal models of immune-system challenge8. Follistatin may also reduce mortality in these animals, due to the neutralization of activin and, thus, increased inflammation8. However, activin may also promote tissue re-modeling. Therefore, follistatin may be used to selectively modulate tissue regeneration, leading to the improved control of wound healing and fibrosis in animals affected by disorders of the relevant processes8. Few formal studies have been conducted to elucidate the pharmacokinetics or pharmacodynamics of FS-344. However, a study of the same of the splice-variant FS-315 suggests that follistatin exhibits rapid clearance and limited distribution4. Therefore, local (e.g. intramuscular for muscle mass and/or regeneration studies) as opposed to systemic administration may be advisable when incorporating FS-344 into a study.

    References:

    1. Yaden BC, Croy JE, Wang Y, et al. Follistatin: a novel therapeutic for the improvement of muscle regeneration. J Pharmacol Exp Ther. 2014;349(2):355-371.
    2. Michel U, Albiston A, Findlay JK. Rat follistatin: gonadal and extragonadal expression and evidence for alternative splicing. Biochem Biophys Res Commun. 1990;173(1):401-407.
    3. Walker RG, Poggioli T, Katsimpardi L, et al. Biochemistry and Biology of GDF11 and Myostatin: Similarities, Differences, and Questions for Future Investigation. Circulation research. 2016;118(7):1125-1142.
    4. Datta-Mannan A, Yaden B, Krishnan V, Jones BE, Croy JE. An engineered human follistatin variant: insights into the pharmacokinetic and pharmocodynamic relationships of a novel molecule with broad therapeutic potential. J Pharmacol Exp Ther. 2013;344(3):616-623.
    5. Shimasaki S, Koga M, Esch F, et al. Porcine follistatin gene structure supports two forms of mature follistatin produced by alternative splicing. Biochem Biophys Res Commun. 1988;152(2):717-723.
    6. Tsuchida K. Myostatin inhibition by a follistatin-derived peptide ameliorates the pathophysiology of muscular dystrophy model mice. Acta Myol. 2008;27:14-18.
    7. Fumagalli M, Musso T, Vermi W, et al. Imbalance between activin A and follistatin drives postburn hypertrophic scar formation in human skin. Experimental dermatology. 2007;16(7):600-610.
    8. de Kretser DM, O'Hehir RE, Hardy CL, Hedger MP. The roles of activin A and its binding protein, follistatin, in inflammation and tissue repair. Molecular and cellular endocrinology. 2012;359(1-2):101-106.
  • GHRP-2 vs GHRP-6

    GHRP-2 and -6 are active in vivo through mimicking ghrelin (green). By own work - adapted from http://www.pdb.org/pdb/files/1p7x.pdb using PyMOL, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4790168 GHRP-2 and -6 are active in vivo through mimicking ghrelin (green). By own work - adapted from http://www.pdb.org/pdb/files/1p7x.pdb using PyMOL, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4790168

    GHRP-2 vs GHRP-6

    Growth hormone releasing peptides (GHRPs) are relatively small molecules associated with the ability to affect the growth hormone secretagogue (GHS) system in some animals. Most GHRPs are made of six amino acids, and were developed with the goal of GHS enhancement and/or study. Their sequences are chosen for the ability to interact with the growth hormone secretagogue receptor (GHS-R) and to elicit some of the downstream effects of growth hormone release (e.g. increased IGF-1 levels). Therefore, either may be useful when applied to studies investigating the various potential roles of the GHS (also known as ghrelin) in mammalian systems. These are thought to include cardioprotection, the prevention of dysfunctional angiogenesis, the control of leptin signalling and cholesterol levels in circulation 1-3. GHRP-2 and GHRP-6 are two particularly well-studied synthetic GHS analogs. They are comparable in size (818 and 873Da respectivelyi,ii). They are both available as high-quality research-grade compunds, available as lyophilized white solidsi,ii. Both peptides are associated with the classic effects of GHS-R activation (i.e. significant increases in GH and IGF-1 concentrations) and may also be associated with significant increases in GHS-R mRNA levels in cardiac tissues4. They have similar sequences, but have structural differences5. Both peptides have been found to act in tandem with GH-releasing factor (GRF or GHRH) to release GH from the rat pituitary5. Both also have a lysine residue at the NH-terminal, although in the case of GHRP-6, this may be substituted for D-Lys, to generate an isoform that antagonizes the GHS-R6. Therefore, GHRP-6 may have a greater range of application compared to GHRP-2.

    Both peptides are thought to be associated with beneficial effects in response to events such as cardiac ischemia, as mentioned above. A study assessed this property using four GHRP variants, including GHRP-2 and (non-DLys) GHRP-6. These were administered subcutaneously to rats that underwent experimentally-induced chronic heart failure, and to identical control animals, at 100µg/kg twice daily for three weeks (or 100µg/kg saline as a placebo). Cardiomyocyte apoptosis (a marker of chronic heart failure) was significantly increased in placebo-treated animals compared to those treated with both GHRP-2 and GHRP-64. Treatment with both ghrelin mimetics also resulted in significant decreases in the stress-related hormones norepinephrine and renin compared to placebo-treated and control animals.  GHRP-2 and -6 also had similar and significant effects on the levels of atrial natriuretic peptide, aldosterone and angiotensin-II compared to placebo-treated animals4. The two peptides also exhibited significant decreases in the abnormal left ventricular dimensions associated with chronic heart failure when compared to that in placebo-treated animals4. Treatment with both peptides also resulted in significantly improved ejection fractions compared to placebo4. Both peptides were also associated with non-significant improvements in diastolic wall (albeit posterior only) thickness post-surgery compared to placebo-treated animals. Both peptides elicited similar effects on GH, IGF-1 and the GSH-R concentrations in experimental animals, as might be expected4. These results indicate that GHRP-2 and -6 demonstrated similar abilities to improve cardiac function by significantly reducing stress and cardiomyocyte death in a model of chronic heart failure. However, neither peptide was associated with significant heart wall remodeling, as may have been expected4.

    In conclusion, GHRP-2 and GHRP-6 may have similar effects in the main locations of the GHS-R, i.e. the pituitary and in cardiac tissues. However, GHRP-6 has greater flexibility in terms of structure and receptor-binding activity when compared to GHRP-2.

    References:

    1. Berlanga J, Cibrian D, Guevara L, et al. Growth-hormone-releasing peptide 6 (GHRP6) prevents oxidant cytotoxicity and reduces myocardial necrosis in a model of acute myocardial infarction. Clinical science (London, England : 1979). 2007;112(4):241-250.
    2. Madhavadas S, Kutty BM, Subramanian S. Amyloid beta lowering and cognition enhancing effects of ghrelin receptor analog [D-Lys (3)] GHRP-6 in rat model of obesity. Indian journal of biochemistry & biophysics. 2014;51(4):257-262.
    3. Zaniolo K, Sapieha P, Shao Z, et al. Ghrelin modulates physiologic and pathologic retinal angiogenesis through GHSR-1a. Investigative ophthalmology & visual science. 2011;52(8):5376-5386.
    4. Xu XB, Pang JJ, Cao JM, et al. GH-releasing peptides improve cardiac dysfunction and cachexia and suppress stress-related hormones and cardiomyocyte apoptosis in rats with heart failure. American journal of physiology. Heart and circulatory physiology. 2005;289(4):H1643-1651.
    5. Cheng J, Wu TJ, Butler B, Cheng K. Growth hormone releasing peptides: a comparison of the growth hormone releasing activities of GHRP-2 and GHRP-6 in rat primary pituitary cells. Life sciences. 1997;60(16):1385-1392.
    6. Luque EM, Torres PJ, de Loredo N, et al. Role of ghrelin in fertilization, early embryo development, and implantation periods. Reproduction (Cambridge, England). 2014;148(2):159-167.
    7. GHRP-2 Product Page. Bluesky Peptides. 2016
    8. GHRP-6 Product Page. Bluesky Peptides. 2016

Items 1 to 10 of 62 total

Page:
  1. 1
  2. 2
  3. 3
  4. 4
  5. 5
  6. ...
  7. 7
Contests & Discounts Newsletter
Free Shipping & HandlingFree Shipping & Handling
My Cart

You have no items in your shopping cart.

My Points

Please log-in or create an account, to use your points.
$
Subscribe & get 35% discount!
get the first offers and events from our store