MOD GRF (1-29)

MOD GRF (1-29) 

Peptide Growth hormone releasing factor (1-29) (abbreviated as GRF (1-29) or also known under the standardized name Sermorelin) is the “shortest fully functional fragment” of endogenous peptide hormone Growth-hormone-releasing hormone (GHRH; somatocrinin). More specifically, it is a fragment of the amino acid chain of GHRH, which is made up of its amino acids at positions 1-29.

The Mod GRF (1-29) peptide (also known as Modified GRF (1-29) or originally referred to as tetrasubstitued GRF (1-29)) is a modified version of Growth hormone releasing factor (1-29). Specifically, this modification consists in replacing the amino acids located in the 2nd, 8th, 15th & 27th positions of the GRF (1-29) amino acid chain with amino acids more resistant to enzymatic cleavage: While the GRF 1-29 amino acid sequence is Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH₂ the MOD GRF 1-29 sequence is Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH_2. As a result of this modification, the initial half-life of GRF (1-29), which was less than 10 minutes, is extended to a longer half-life of MOD GRF (1-29), which is at least 30 minutes.

MOD GRF (1-29) history

Researchers have found that the first 29 amino acids of the growth hormone releasing hormone (GHRH) amino acid chain provide its full biological activity (a portion of its amino acids at positions 1-29 is as strong and efficient as its full/complete 44 amino acid structure). This fragment (1-29) has been named as Growth hormone releasing factor (1-29) (abbreviated GRF (1-29)). Then, in an effort to enhance the biological activity and reduce the rapidity of metabolic clearance, the development of more efficient analogs and modified versions of GRF (1-29) continued. These analogues were primarily created by substituting amino acids within the peptide structure for amino acids more resistant to enzymatic cleavage and degradation.

One of the first modified analogues of GRF (1-29) substituted the amino acid L-alanine (Ala) at the 2nd position of the peptide structure for its optical isomer (mirror image) D-alanine (D-Ala), what led to a peptide bond between D-Ala and the 3rd amino acid in the structure – aspartic acid (Asp). The result was higher ability to resist rapid cleavage by the enzyme dipeptidyl peptidase-4 (a cleavage which had previously led to change of unmodified GRF (1-29) to an inactive peptide fragment). Based on this successful modification, other analogs with further amino acid substitutions were then developed.

For the first time, mention of tetrasubstituted GRF (1-29) appeared in a scientific study of GRF (1-29) analogues, that investigated it as one of the studied modified form of GRF (1-29). The term “tetrasubstituted” was used to describe the replacement of amino acids in 2nd, 8th, 15th and 27th positions in the amino acid chain of GRF (1-29). Later in 2008, a scientist acting under the name DatBtrue began using the term MOD GRF (1-29) in his published scientific articles instead of the original name “tetrasubstitued GRF (1-29)”. Then, the term MOD GRF (1-29) started gaining popularity, and due to its frequent use in public and private scientific forums, in the end it became a standard and often used name.

Growth hormone–releasing hormone (GHRH)

Endogenous peptide hormone GHRH (Somatocrinin) is firstly secreted in the pulsatile manner from the arcuate nucleus of the hypothalamus. Then it is transported by the hypothalamic-hypophyseal portal system to the pituitary gland, where it stimulates the production of GH by binding to the GHRH receptors. 

MOD GRF (1-29) Mechanism of action

MOD GRF (1-29), like other GHRH receptor agonists mimics the action of natural endogenous Growth hormone–releasing hormone: In the pituitary, it binds to GHRH receptors and thereby stimulates the production of natural Growth hormone in the body. MOD GRF (1-29), due to its modifications and improved resistance to enzymatic cleavage, stimulates Growth hormone production several times more efficiently and potently than endogenous GHRH. 

MOD GRF (1-29) Results of action

Since the main function of MOD GRF (1-29) (as well as GRHR and its other mimetics) is to stimulate Growth hormone secretion by the pituitary gland, the end results of its activity (or better said, the end results in which it participates) are the final results mediated by Growth hormone activity in the body. Growth hormone (GH) is an important protein hormone in the body involved in many important biological processes and functions (including growth and metabolism). 

Direct effects of Growth hormone are mediated by its binding to the receptors on the target cells. For example, adipocytes (fat cells) have growth hormone receptors and GH stimulates them to cleave triglycerides and supresses their ability to absorb and accumulate circulating lipids. Indirect effects of Growth hormone are mediated by a insulin-like growth factor-1 (IGF-1) activity, a hormone that is secreted from the liver and other tissues in response to growth hormone (GH stimulates the production of IGF-1 through the JAK-STAT signaling pathway).

Most of the growth promoting effects of GH is actually due to IGF-1 acting on its target cells. Main direct and indirect effects and functions related with Growth hormone include proliferation & differentiation of chondrocytes (cartilage cells) resulting in bone growth in childhood; cell growth and regeneration in the whole body; stimulation of amino acid uptake and protein synthesis in muscle and other tissues; important effects on protein, lipid and carbohydrate metabolism; or roles in cognition, neurogenesis, and neuronal survival.

MOD GRF (1-29) vs. CJC-1295 differences

Both peptides MOD GRF (1-29) and CJC-1295 are synthetic anologues of growth hormone releasing hormone (GHRH); and modified / more potent versions of GRF (1-29), act on the same target receptor (GHRHR) and stimulate and amplify the pulsatile release of the growth hormone, but the main and big difference between them is their biological hal-life and duration of their action in the body: While MOD GRF (1-29) has relative shorter half-life just above 30 minutes, CJC-1295 (DAC-GRF) has extremely prolonged half-life to 6-10 days. In this case, the shorter half-life of MOD GRF (1-29) reflects a much more accurately natural model of action of endogenous GHRH, what can prevent certain unwanted side effects especially during long-term use.

Scientifically investigated possible benefits of MOD GRF (1-29)

• • MOD GRF (1-29) stimulates and amplify the secretion of growth hormone
  • MOD GRF (1-29) improves overall regeneration and cellular repair 
  • MOD GRF (1-29) stimulates protein synthesis and supports muscle mass growth
  • MOD GRF (1-29) has important effects on protein, lipid and carbohydrate metabolism
  • MOD GRF (1-29) increases fat utilization by stimulating triglyceride breakdown & oxidation in adipocytes
  • MOD GRF (1-29) helps to increase calcium retention and bone mineralization
  • MOD GRF (1-29) may help reduce the risk of cardio-vascular diseases
  • MOD GRF (1-29) supports cognitive and brain functions
  • MOD GRF (1-29) helps strengthen the immune system
  • MOD GRF (1-29) promotes a sense of energy and vitality
  • MOD GRF (1-29) provides anti-aging effects

MOD GRF (1-29) possible side-effects

• • MOD GRF (1-29) may cause tingling sensation in the feet and hands
  • MOD GRF (1-29) may cause slight irritation on the injection site
  • MOD GRF (1-29) may cause joint pain
  • MOD GRF (1-29) may cause water retention
  • MOD GRF (1-29) may cause low blood sugar
  • MOD GRF (1-29) may reduce insulin sensitivity

MOD GRF (1-29) dosage

In the scientific studies and clinical trials performed, the dosage used is often referred to as 1-3 mcg of MOD GRF (1-29) per 1 kg body weight, 1-3 times a day. For multiple doses, it is appropriate to distribute them equally over time throughout the day, to mimic the natural, pulsed release of natural growth hormone throughout the day. Administration of MOD GRF (1-29) alone may not significantly increase growth hormone secretion. Therefore, it is often combined with administration of GHRPs such as Ipamorelim, GHRP-6, GHRP-2 or Hexarelin to ensure a significant increase in GH production, and at the same time, their combination works synergistically and greatly increases their effectiveness with each other.

Overview

MOD GRF (1-29) (also called as Modified GRF (1-29), tetrasubstitued GRF (1-29) or modified Growth hormone releasing factor (1-29)) is a modified version of Growth hormone releasing factor (1-29) and synthetic analogue of endogenous peptide hormone GHRH. This modification consists in replacing the amino acids located in the 2nd, 8th, 15th & 27th positions of the GRF (1-29) amino acid chain with amino acids more resistant to enzymatic cleavage. As a result of this modification, the half-life is extended to 30 minutes. MOD GRF (1-29) mimics the action of natural endogenous Growth hormone–releasing hormone, in the pituitary binds to GHRH receptors and thereby stimulates the secretion of natural Growth hormone. The end results in which MOD GRF (1-29) participates are the final results mediated by Growth hormone activity in the body, and include proliferation & differentiation of chondrocytes (cartilage cells) resulting in bone growth in childhood; cell growth and regeneration in the whole body; stimulation of amino acid uptake and protein synthesis in muscle and other tissues; important effects on protein, lipid and carbohydrate metabolism; or roles in cognition, neurogenesis, and neuronal survival.