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Sermorelin - synthetic version of the peptide hormone GHRH

Sermorelin is a synthetic version of the peptide hormone GHRH and can be considered interchangeable where acute effects of either are studied. Sermorelin is also referred to as GHRH (1-29) or GRF 1-29 because the peptide chain contains 29 aminos as opposed to the 44 in native GHRH. Native GHRH is produced in and released from the hypothalamus. GHRH causes the anterior pituitary’s somatotropes to release growth hormone, and also directly (by other mechanisms) promoted slow-wave sleep.[1] GHRH is released in pulses in the body that alternate with corresponding pulses of somatostatin or growth-hormone inhibiting-hormone. Somatostatin causes the pituitary to cease release of growth hormone. Ghrelin, released from the gut which circulates and acts as a hunger hormone, has synergistic activity in the body with GHRH and also suppresses somatostatin to make way for the GHRH pulse. If exogenous GHRH (sermorelin) is administered when somatostatin is active, it has no effect. Another difference between GHRH and sermorelin is that while an acute dose of either has the same effect, the pulse pattern of native GHRH – longitudinal release or release over time – is different from a single administration of sermorelin. To compensate for this difference in studies and in clinical uses, multiple injections of sermorelin are used, or sometimes sermorelin is administered from an intravenous pump device.

The effectiveness of peptides such as sermorelin for GH replacement therapy is generally greater than that of exogenous synthetic 22kDa growth hormone, attributable primarily to the pulsatility of the GH release induced (3 hour duration as opposed to 8 hour duration), or “spontaneity” as Lebl’s Czech study refers to it:

BACKGROUND: Treatment with growth hormone (GH) restores the natural growth rate in children with growth hormone deficiency (GHD). This is, however, achieved only after daily injections extending over many years and therefore daily short-term hypersomatotropinaemia. Stimulation of endogenous secretion of GH e.g. by oral administration of growth hormone-releasing peptide (GHRP) may help in future to eliminate these adverse aspects. This treatment could be beneficial in patients with a stimulable endogenous GH secretion. METHODS AND RESULTS: In order to find potential candidates for spontaneous secretion of GH the authors examined, using a test with sermoreline (GHRH1-29NH2), 31 children (21 boys) aged 5.8-16.5 years suffering from idiopathic (GHD), previously treated by daily GH injections. GH rose after stimulation with sermoreline to more than 14 mIU/l in 18/31 children (responders). The ratio of "responders" was higher in the sub-group of children with isolated GHD, as compared with multiple pituitary deficiency (p = 0.05) and insignificantly higher in the sub-group of children born by breech delivery (p = 0.13). CONCLUSIONS: More than half the children treated nowadays with GH could profit in future from the method of spontaneous GH secretions. The success of this procedure is more likely in children with isolated GHD and in breech delivered children.[2]

Because GH release varies greatly from person to person and in different life stages, and because different persons have different levels of cellular sensitivity to GH, one test used by practitioners to test for GH deficiency in short-stature children is to measure plasma blood levels and then administer GHRH and retest, in order to compare the “baseline” to an optimized release pattern for that particular individual:

Sermorelin is a well tolerated analogue of GHRH which is suitable for use as a provocative test of growth hormone deficiency when given as a single intravenous 1 microg/kg bodyweight dose in conjunction with conventional tests. Limited data suggest that once daily subcutaneous sermorelin 30 microg/kg bodyweight is effective in promoting growth in some prepubertal children with idiopathic growth hormone deficiency.[3]

Future therapies will likely include combined use of one of several GHRPs as well as sermorelin or a similar analog due to the necessity of inhibiting somatostatin for GHRH to work, as well as due to the overall synergy and efficacy as demonstrated in the following study by Pandya et al (note that endogenous GHRH is somewhat interchangeable with exogenous, if one adjusts to mimic release patterns in regards to administration of the synthetic version):

GH-releasing peptide-6 (GHRP-6) is a potent GH secretagogue that releases GH by uncertain mechanisms. To assess whether GHRH is required for GH release by GHRP-6 in humans, we used the specific antagonist to GHRH (N-Ac-Tyr1,D-Arg2)GHRH(1-29)NH2 (GHRH Ant). We have previously shown that GHRH-Ant (400 microg/kg) blocked the GH response to 0.33 and 3.3 microg/kg boluses of GHRH by 95% and 81%, respectively. Nine healthy men between the ages of 20 and 30 yr were studied on two occasions. They received either saline or GHRH-Ant (400 microg/kg, i.v.) at 0840 h, followed by GHRP-6 (1 microg/kg, i.v. bolus) at 0900 h. Blood was sampled every 10 min from 0800-1100 h. GH responses were measured as the maximal increase over the baseline GH concentration and as the area under the curve. GHRH-Ant eliminated most of the GH response to GHRP-6 [maximal increase over the baseline GH concentration, 33.8 +/- 4.8 vs. 6.2 +/- 1.8 microg/L (mean +/- SEM; P < 0.0001); area under the curve, 1701 +/- 278 vs. 376 +/- 113 microg/min x L (P < 0.001)]. These data show that endogenous GHRH is necessary for most of the GH response to GHRP-6 in humans.[4]

Sermorelin References:

[1] Obál F, Krueger J (2001). "The somatotropic axis and sleep.". Rev Neurol (Paris) 157 (11 Pt 2): S12–5.

[2] Lebl J, Pechová M. [Stimulation of endogenous secretion of the growth hormone. Today in diagnosis, tomorrow in therapy?] Cas Lek Cesk. 1995 Jun 14;134(12):371-3.

[3] Prakash A, Goa KL. Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs. 1999 Aug;12(2):139-57.

[4] 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.
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