Introduction.
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 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 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, GIT (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.
Selected
Studies.
The two studies reviewed hereafter
have provided adequate and conclusive findings that sermorelin can be used
clinically to promote growth and manage GHRH deficiency.
1.
Sermolelin 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 intravenous sermorelin injection 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 the intravenous and
subcutaneous 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 sermorelin injection 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.
2.
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 ®) injection 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 Sermorelin can be used 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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