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CJC-1293 (GRF [1-29]) 2000mcg

 [CJ93]
 $45.00 
CJC-1293 (GRF [1-29]) 2000mcg

CJC-1293 Modified GRF (1-29)

In the healthy human body, large amounts of growth hormone are stored in the pituitary.  The cells within the pituitary release growth hormone in response to signaling by GHRH (Growth Hormone Releasing Hormone), Ghrelin (of which GHRPs - Growth Hormone Releasing Peptides - are mimetics), and are inhibited from releasing these stores by Somatostatin.  GHRH and Ghrelin act on different populations of somatotropes (GH releasing cells).  GHRP/Ghrelin increases the number of somatotropes releasing GH but not the amount released by each cell; GHRH affects both the number of secreting cells and - more so - the amount they each secrete. [1] GHRH and Ghrelin are released in specific patterns that vary depending on event and environment: post-exercise, in response to slow wave sleep, in certain stages of life and physical development, and so on.

 

Most people (even the diseased) continue to possess the ability to make GH in the pituitary. The problem is in the signalling of the pituitary to release it and make more.  Even most people with diseases that affect growth hormone secretion retain the ability to continue to make GH in their pituitaries.  The disease states and symptoms result, most typically, in altered (dysfunctional) GH release signaling and this also affects the ability of the pituitary to continue to make more GH. [2]

 

Endogenous-type GHRH, which has a forty-four amino acid long chain (and a specific shape - thus making it a peptide as well as a hormone), has been marketed for the longest as Sermorelin in comparison to the other GHRH-type peptides.  However, Sermorelin has been demonstrated to be degraded rapidly in the body and is cost-inefficient.  But because most patients in need of GH therapy do retain the ability to produce and secrete their own GH, treatment with a GHRH-type analog remained hypothetically preferable to exogenous  GH treatment.  GH itself when administered exogenously results not only in "unnatural" release patterns, it results universally in down regulation of endogenous GH production - as do many hormones when applied exogenously.[3]

 

Sermorelin's limitations naturally resulted in a variety of formulations of GHRH analogs for therapeutic usage.  CJC-1295, discussed in another article, is a GHRH analogue with attached MPA (aka DAC), binds to albumin in the bloodstream and circulates for a week or longer.  Modified GRF 1-29, which is also called D-Ala2-GHRH-(1-29), [Nle27]-hGHRH(1-29)-NH2, GHRH (1-29)NH2, or ModGRF1-29, is the bioactive portion of GHRH(1-44) with fifteen amino acids subtracted and four amino acids replaced at the weakest points in the peptide structure.

 

Soule et al write that "D-Ala2 substitution contributes to the enhancement of biological activity by reducing metabolic clearance." [3]  In a comparison study with synthetic exogenous GH for treating prepubertal GH deficiency, Lanes and Carillo concluded that "GHRH (1-29) at the dose and schedule used is generally effective in the treatment of GH deficiency." [4]

 

Campbell et al explain both GHRH(1-44)'s shortcomings in treatment as well as advantages offered by Modified GRF (1-29) and specific structural differences:

Native human GRF(1-44)-NH2(hGRF44) is subject to biological inactivation by both enzymatic and chemical routes. In plasma, hGRF44 is rapidly degraded via dipeptidylpeptidase IV (DPP-IV) cleavage between residues Ala2 and Asp3. The hGRF44 is also subject to chemical rearrangement (Asn8-->Asp8, beta-Asp8 via aminosuccinimide formation) and oxidation [Met27-->Met(O)27] in aqueous environments, greatly reducing its bioactivity. It is therefore advantageous to develop long-acting GRF analogues using specific amino acid replacements at the amino-terminus (to prevent enzymatic degradation): residue 8 (to reduce isomerization) and residue 27 (to prevent oxidation). Inclusion of Ala15 substitution (for Gly15), previously demonstrated to enhance receptor binding affinity, would be predicted to improve GRF analogue potency. Substitution of [His1,Val2]-(from the mouse GRF sequence) for [Tyr1,Ala2]-(human sequence) in [Ala15,Leu27]hGRF(1-32)-OH analogues completely inhibited (24-h incubation) DPP-IV cleavage and greatly increased plasma stability in vitro. Additional substitution of Thr8 (mouse GRF sequence), Ser8 (rat GRF sequence), or Gln8 (not naturally occurring) for Asn8 (human GRF sequence) resulted in analogues with  enhanced aqueous stability in vitro (i.e., decreased rate of isomerization). These three highly stable and enzymatically resistant hGRF(1-32)-OH analogues, containing His1, Val2, Thr/Gln8, Ala15, and Leu27 replacements, were then bioassay for growth hormone (GH)-releasing activity in vitro (rat pituitary cell culture) and in vivo (SC injection into pigs). Enhanced bioactivity was observed with all three hGRF(1-32)-OH analogues. In vitro, these analogues were approximately threefold more potent than hGRF44, whereas in vivo they were eleven- to thirteen fold more potent.[5]

 

Just as GHRH and Ghrelin work in conjunction through different means for maximal GH release within the body, exogenous GHRH such as Modified GRF (1-29) results in a synergistic effect when used with a Ghrelin mimetic, such as the hexapeptide known as GHRP-6. [6] Pandya et al also conclude that "GHRH is necessary for most of the GH response to GHRP-6 in humans." [6]  Massoud et al conclude that "Hexarelin and GHRH-(1-29)-NH2 are synergistic" [7]  (Ed note: Hexarelin is another Ghrelin mimetic).

 

Sawada writes that  "findings suggest that the KP-102-induced GH secretion largely depends on GRF and the secretagogue potentiates the GRF effect by antagonizing the SS action at the level of somatotropes. It is concluded that KP-102 alone or in combination with GRF provides a means of stimulating GH secretion in the face of elevated inhibitory tone mediated by SS." [8] (Ed note: KP-102 is the Ghrelin mimetic GHRP-2)

 

An abstract of a review by Hamilton touches on the main advantage of GRF(1-29) over, for example, CJC-1295 or synthetic GH:

...growth hormone secretion occurs in a rhythmic pattern regulated by intricate interactions between two neurohormones: growth hormone-releasing hormone (GHRH) and somatotropin release-inhibiting factor (SRIF).[...] research also indicates that there are sexual differences in the pattern of growth hormone release and that growth hormone regulates its own secretion by means of a negative feedback system. [9]

 

By mimicking natural release patterns with properly dosed and timed GHRPs (Ghrelin mimetics) and GHRH-analogues, negative feedback and undesirable side effects that are typically seen in synthetic GH therapy or even with past forms of GHRH administration (such as constant low-dose administration via pump) can be avoided.

 

For achieving ends other than restoring natural GH release in diseased patients, optimized rhythmic or pulsatile dosing of GHRH with or without a GHRP may be useful, as Vittone et al write about their findings on GHRH applied to healthy elderly men:

...data suggest that single nightly doses of GHRH are less effective than multiple daily doses of GHRH in eliciting GH- and/or IGF-I-mediated effects. GHRH treatment may increase muscle strength, and it alters baseline relationships between muscle strength and muscle bioenergetics in a manner consistent with a reduced need for anaerobic metabolism during exercise. Thus, an optimized regimen of GHRH administration might attenuate some of the effects of aging on skeletal muscle function in older persons.[10]

 

Cititations

[1] Lewis UJ. Growth hormone: what is it and what does it do? Trends Endocrinol Metab 1992;3:117–121

[2] J Izdebski, J Pinski, JE Horvath, G Halmos, K Groot and AV Schally.  Synthesis and Biological Evaluation of Superactive Agonists of Growth Hormone-Releasing Hormone. Proceedings of the National Academy of Sciences, Vol 92, 4872-4876.

[3] Soule S, King JA, Millar RP.  Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men.  J Clin Endocrinol Metab. 1994 Oct;79(4):1208-11.

[4]Lanes R, Carrillo E.  Long-term therapy with a single daily subcutaneous dose of growth hormone releasing hormone (1-29) in prepubertal growth hormone deficient children. J Pediatr Endocrinol. 1994 Oct-Dec;7(4):303-8.

[5] Campbell RM, Stricker P, Miller R, Bongers J, Liu W, Lambros T, Ahmad M, Felix AM, Heimer EP. Enhanced stability and potency of novel growth hormone-releasing factor (GRF) analogues derived from rodent and human GRF sequences. Peptides. 1994;15(3):489-95.

[6]Pandya N, DeMott-Friberg R, Bowers CY, Barkan AL, Jaffe CA. Growth hormone (GH)-releasing peptide-6 requires endogenous hypothalamic GH-releasing hormone for maximal GH stimulation. J Clin Endocrinol Metab. 1998 Apr;83(4):1186-9.

[7]Massoud AF, Hindmarsh PC, Matthews DR, Brook. The effect of repeated administration of hexarelin, a growth hormone releasing peptide, and growth hormone releasing hormone on growth hormone responsivity.  Clin Endocrinol (Oxf). 1996 May;44(5):555-62.

[8] Sawada H. Effect of newly developed analogue of growth hormone releasing peptide [D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2 (KP-102)] on growth hormone secretion in adult male rats (Trans. from Japanese). Nippon Ika Daigaku Zasshi. 1995 Apr;62(2):142-9.

[9] Hamilton J. A question of rhythm: recent advances in growth hormone research. CMAJ. 1995 Sep 1;153(5):585-8.

[10] Vittone J, Blackman MR, Busby-Whitehead J, Tsiao C, Stewart KJ, Tobin J, Stevens T, Bellantoni MF, Rogers MA, Baumann G, Roth J, Harman SM, Spencer RG. Effects of single nightly injections of growth hormone-releasing hormone (GHRH 1-29) in healthy elderly men. Metabolism. 1997 Jan;46(1):89-96.

 

*The latter article is intended for educational / informational purposes only. THIS PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. Bodily introduction of any kind into humans or animals is strictly forbidden by law.

 

This product was added to our catalog on Saturday 08 November, 2008.
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  CJC 1295 DAC, 2000mcg
 
 

CJC 1295 DAC, 2000mcg

Works as promised. No need to worry about quality. All of Iron D'...
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