Active Substance: Grf 1-29
Brand: Europe Pharmaceutical
GRF (1-29) is a peptide hormone of the GHRH class, which increases the synthesis of growth hormone in the body. This peptide, most often, is sold under the trademark Sermorelin (Sermorelin).
GRF 1-29 (Sermorelin) by Europe Pharmaceutical
GRF 1-29 Sermorelin is a GHRH (growth hormone–releasing hormone) peptide analogue. Its peptide sequence is comprised of 29 amino acids. This sequence is a portion of the endogenous human GHRH, and is currently considered to be the shortest synthetic peptide that possesses the full array of functional GHRH activity. Due to this fact, sermorelin is considered to be a growth hormone secretagogue.
Sermorelin has been used during research to stimulate the secretion of growth hormone from the adenohypophysis (also called the anterior pituitary). The anterior pituitary secretes trophic hormones. Sermorelin has also been used in research stimulation tests to assess for pituitary sufficiency in relation to the secretion of the growth hormone.
Growth hormone–releasing hormone
GHRH is 44 amino-acids polypeptide that stimulates the secretion of growth hormone from the adenohypophysis. It is also called somatocrinin or somatoliberin. It is produced in the cell bodies of periventricular arcuate neurons, and thereafter transported to the neurosecretory terminals of the neurons where they are released. The arcuate neurons do form part of the hypothalamo-hypophyseal portal system. Their release from the neurosecretory terminals occur in a pulsatile fashion and it thus follows that growth hormone (GH) release also occurs in a corresponding pulsatile fashion. GHRH binds to a secretin-type G-protein coupled serpentine receptor called the GHRH-receptor (GHRHR). Binding causes the receptor to activate both the cAMP (cyclic Adenosine Monophosphate)-dependent pathway and the phospholipase C (PLC) pathway. The terminal downstream actions of the cAMP-dependent pathway do upregulate the transcription of both the GH and GHRHR genes thereby providing a positive feedback loop that amplifies the production of GH. The GH produced is thereafter packaged in secretory vesicles. The downstream actions of the PLC pathway results in both Na+-voltage-dependent and Ca2+-dependent fusion of the secretory vesicles with the plasma membrane thereby releasing GH into the bloodstream.
The actions of GH ensure an optimal well-regulated post-natal growth. GH also promotes efficient energy metabolism. Studies have also shown that GHRH directly promotes slow wave NREM (non-rapid eye movement) sleep, and thus GHRH insufficiency causes a reduction in the amount and intensity of slow wave NREM sleep which results in either insomnia or dysomnia (sleep disorders that causes sleep to lose its restorative capacity). Studies have also shown that GHRH inhibits the actions of somatostatin. Somatostatin is a polypeptide hormone that inhibits GH secretion from the adenohypophysis. Both GHRH and somatostatin are produced in the same neuron but they are released in alternation to each other thereby resulting in the pulsatile release of GH from the neuron.
Recent research has also shown that GHRH is also produced outside the hypothalamus by pancreatic cells, gastrointestinal tract epithelial cells and in some neoplastic cells. Clinical studies have also shown that the actions of Sermorelin are similar to the GHRH actions. Thus, Sermorelin has been used to diagnose deficiencies in GH secretions. Also, Sermorelin has been investigated for its therapeutic properties as the studies discussed below show.
The two studies reviewed hereafter have provided adequate and conclusive findings that sermorelin can be used clinically to promote growth and manage GHRH deficiency.
- Sermorelin and growth hormone (GH) deficiency.
In 1999, a study entitled “Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency” was authored by Aitabh Prakash and Karen Goa and published in the journal Biodrugs. The aim of this study was to investigate whether sermorelin injection stimulates GH secretion from the adenohypophysis. The subjects of this study included adults and pre-pubertal children (both normal and those suffering from GH deficiency). The subjects were randomly divided into two groups with one group receiving intravenous sermorelin injection and the other group receiving subcutaneous sermorelin injection.
The results obtained from both groups showed that GRF 1-29 was able to rapidly diagnose GH insufficiency in children affected by GH deficiency (p < 0.05). The p<0.05 is a measure of statistical significance, and the value 0.05 shows that the results are statistically significant. However, the diagnosis could only isolate GH insufficiency caused by GHRH deficiency. The results also revealed that subcutaneous sermorelin injection did cause a significant increase in height in children suffering from idiopathic GH deficiency, and that this acceleration in growth rate could be maintained consistently for 36 months. Likewise, the results also revealed that both Sermorelin administrations were well tolerated with the only observable adverse effects being injection-site pain and transient facial flushing.
In summary, the findings of this study show that GRF 1-29 stimulates GH secretion from the adenohypophysis. Also, intravenous sermorelin can be used to diagnose some cases of GH deficiency, and subcutaneous sermorelin can be used to manage GH insufficiency.
- Sermolelin and growth acceleration in a chronic disease state.
In 1996, Pasqualini et al conducted a study that was published under the title “Growth acceleration in children with chronic renal failure treated with growth-hormone-releasing hormone (GHRH)” in the journal Medicina. The subjects involved in this study were 9 children aged between 1 to 14 years old. They all suffered from chronic renal failure (CRF). The aim of this study was to investigate whether subcutaneous Sermorelin causes growth increase in children ailing from CRF. The subjects were categorized into 3 groups, the first group comprised of 3 children on conservative management, the second group comprised of 3 children on dialysis and the last group comprised 3 children who had undergone renal transplantation. Each of the three groups was administered with subcutaneous Sermorelin acetate (Geref ®) for a period of 3-6 months.
The results showed that the mean serum creatinine and urea levels remained stable in all the subjects except for two children on conservative management who showed an increase in their serum creatinine levels. The results also revealed that the rate of height increase in 5 of the subjects (3 on conservative management, one on dialysis and the other had undergone transplantation) averaged about 4.2cm/year (p < 0.05). Also, Geref® caused a higher peak in GH response among growth non-responders as compared to the growth responders (p < 0.05). The results obtained in this study do show that non-responders suffered from GH-resistance as demonstrated by the fact that they had high levels of GH but their growth was still stunted.
In summary, the findings of this study show that sermorelin does increase the rate of growth in GH-responsive CRF children, though it has no appreciable effect on the course of the CRF.
In conclusion, the above two studies show that GRF 1-29 can be used in research to diagnose cases of GH deficiency, stimulates GH secretion from the adenohypophysis, manage GH insufficiency and increase the rate of growth in GH-responsive CRF children.
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