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