Sermorelin – an overview | ScienceDirect Topics

B.L. Furman, in Reference Module in Biomedical Sciences, 2017

Sermorelin is very rapidly cleared from the plasma due to degradation. Amino acid substitutions reduce clearance and prolong the disappearance half time Soule et al. (1994).

Sermorelin activates anterior pituitary receptors for growth hormone-releasing hormone (GHRH).

Sermorelin is licensed as a diagnostic test for secretion of growth hormone. It is also used for the treatment of growth hormone deficiency in children. However, products containing sermorelin were withdrawn from the United States market by the manufacturer in November 2002.

Pregnancy and breast-feeding. It should be used with caution in epilepsy or in untreated hypothyroidism and in the presence of obesity, hyperglycemia, or elevated plasma fatty acids.

Occasional facial flushing and pain at injection site.

In cells cultured from rat pituitaries, sermorelin was extremely potent in stimulating the secretion of growth hormone, with a minimal effective dose of 0.4 X 1015 M Heiman et al. (1985).

No human pharmacokinetic studies appear in the literature. After IV injection in the rat, the half-life of sermorelin was around 6.2min (Rafferty et al., 1988).

Mark T. Keegan, in Pharmacology and Physiology for Anesthesia (Second Edition), 2019

Sermorelin acetate is a synthetic analog of GHRH also available for treatment of GH deficiency. It is less effective than GH and not suitable for GH deficiency of pituitary origin. Recombinant human IGF-1 is also available for use in patients with GH resistance. Mecasermin is a complex of recombinant human IGF-1 and recombinant human IGF-binding protein-3 (rhIGFBP-3) used to treat children with severe IGF-1 deficiency unresponsive to GH. The rhIGFBP-3 is used to maintain an adequate half-life of the biologically active IGF-1. Subcutaneous administration can cause hypoglycemia and so should be given only around food ingestion. Elevations in intracranial pressure and liver blood tests can also occur. Pegvisomant is a GH receptor antagonist used in the treatment of acromegaly.65 It is administered subcutaneously once daily with dosage adjusted to serum IGF-1 levels. It can cause liver dysfunction and, theoretically, loss of negative feedback of GH and IGF-1 can lead to increased growth of GH-secreting tumors. Tesamorelin is an analog of GHRH used to treat HIV-associated lipodystrophy.

Mark Kester PhD, ... Kent E. Vrana PhD, in Elsevier's Integrated Review Pharmacology (Second Edition), 2012

Sermorelin, somatropin, and mecasermin are given for growth hormone deficiency syndromes, and lanreotide, octreotide, and pegvisomant are used to treat growth hormone excess.

Growth hormonereleasing hormone induces the anterior pituitary to secrete growth hormone (somatotropin). Growth hormone induces its own feedback inhibition by stimulating growth hormone inhibitory hormone (somatostatin) release from the hypothalamus (Fig. 12-6). Recombinant DNA versions of growth hormone (somatotropin) can be used to treat growth hormone deficiency (dwarfism). Several different recombinant products are available and differ from in terms of route of administration (intramuscular or subcutaneous) and frequency of injection (three to seven times per week). A growth hormonereleasing hormone biologic, sermorelin (consisting of the first 29 amino acids of growth hormonereleasing hormone), is available for patients who have a hypothalamic deficiency. In addition, an insulinlike growth factor therapy, mecasermin, has been approved for children who may not necessarily have a growth factor deficiency but may be resistant to the effects of growth hormone due to the production of neutralizing antibodies to growth hormone. Mecasermin is also used for children with severe insulinlike growth factor-1 deficiency. Mecasermin is administered subcutaneously before meals to avoid a hypoglycemic response. This is yet another example of how targeting a signal transduction cascade (insulinlike growth factor-1 tyrosine kinase receptors) yields a novel therapeutic strategy.

Figure 12-6. Growth hormone feedback inhibition. GHIH, growth hormone inhibitory hormone (somatostatin); GHRH, growth hormonereleasing hormone.

In contrast, synthetic forms of growth hormone inhibitory hormone (somastatin), such as lanreotide and octreotide, are effective for managing growth hormone excess (acromegaly or gigantism). Acromegaly is often the result of a benign pituitary tumor; pharmacologic treatment is often initiated because of inadequate responses to surgery and radiation. These biologics are 40 times more potent at inhibiting growth hormone secretion than is endogenous somatostatin. However, subcutaneously administered lanreotide and intramuscularly administered octreotide are associated with abdominal cramps, reduced gallbladder contractility, gallstones, reduced serum levels of vitamin B12, and altered absorption of dietary fats. A newer, more specific therapy uses a growth factor receptor antagonist such as pegvisomant to treat acromegaly. Injection site reactions, flulike symptoms, diarrhea, and elevated liver enzyme levels can occur. Hepatoxicity must therefore be closely monitored.

Elvira Rodriguez-Pinilla, Corinna Weber-Schndorfer, in Drugs During Pregnancy and Lactation (Second Edition), 2007

Synthetic analogs are sermorelin and somatorelin. These hormones reduce blood flow to the uterus and inhibit endometrial proliferation. For these reasons, they are used preoperatively in treating uterine leiomyomata. In case of inadvertent use during pregnancy, miscarriage and fetal growth restriction are conceivable; however, these effects have not been reported to date.

Somatostatin inhibits the release of both growth hormone and TSH. In this respect, it is unique among the hypothalamic hormones. Therapeutically, it is used for carcinoids and to lower the growth hormone concentration in acromegaly. A synthetic octapeptide derivative of somatostatin, octreotide, is available for therapeutic use. In a few individual cases octreotide was used during a part of pregnancy or throughout pregnancy for treatment of acromegaly; no malformations or other adverse effects were reported (Cozzi 2006, Blackhurst 2002, Neal 2000, Takeuchi 1999, Colao 1997). It was reported that ultrasound monitoring of fetal parameters during octreotide long-acting repeatable treatment in a patient suggested the possibility of fetal growth retardation, prompting drug dosage decrease (Fassnacht 2001). However, experience with use of octreotide during pregnancy is insufficient for a well-grounded assessment of the teratogenic potential. There is no experience with exposure during pregnancy with lanreotide, an analog of somatostatin or with pegvisomant, a somatotropin receptor antagonist.

Recommendation.

There are only rare indications for using hypothalamic releasing hormones during pregnancy. Inadvertent use is not grounds for either termination of the pregnancy or invasive diagnostic procedures.

John J. Kopchick, ... Lawrence A. Frohman, in Endocrinology: Adult and Pediatric (Seventh Edition), 2016

The potency of the two naturally occurring analogues of GHRH, GHRH(140)-OH and GHRH(144)-NH2 and the truncated GHRH(1-29)-NH2(sermorelin)335 has been compared and found to be equal. Of these three compounds, only sermorelin has been approved for clinical use. However, it has been withdrawn by the manufacturer and is not commercially available in the United States. Another GHRH analogue, tesamorelin, described under therapeutic uses of GHRH, has not been evaluated for diagnostic use as a GH secretagogue.

Zhifang Xu, in Handbook of Hormones, 2016

Mutations in the GHRH gene have never been described. A single base change in the GHRH-R gene in human somatotropinomas confers hypersensitivity to GHRH binding. Pit-1 mutation inducing the low gene expression of GHRH-R can lead to development of dwarfism [12].

Sermorelin, a functional peptide fragment of GHRH129, has been used in the diagnosis and treatment of children with idiopathic growth hormone deficiency [13]. Tesamorelin, a stabilized synthetic peptide analog of GHRH144, received US Food and Drug Administration approval in 2010 for the treatment of lipodystrophy in HIV patients under highly active antiretroviral therapy, and was investigated for effects on certain cognitive functions in adults with cognitive impairment and healthy older adults [4].

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Sermorelin - an overview | ScienceDirect Topics