Pharmacologic Class: Sermorelin is the structurally truncated analog of Growth Hormone Releasing Hormone (GHRH). It consists of the first 29 amino acids of the naturally occurring neurohormone that is produced in the hypothalamus.1
Other names: Geref, GRF 1-29
General Information: Sermorelin is the most widely used member of the GHRH analogue drug class. It can significantly promote the synthesis and release of growth hormone (GH) from cells in the pituitary gland, improving the serum concentrations of GH and subsequently insulin-like growth factor 1 (IGF-1) in animals and humans.23 It is able to influence the concert of hormonal signals that affect GH secretion from the anterior pituitary including GHRH, somatostatin, and insulin like growth factor (IGF) and others. The positive and negative opposing regulation of growth hormone by GHRH and somatostatin, respectively, creates a rhythmic-circadian pattern of GH secretion.4 Thus, modification of both pulse amplitude and frequency of GH secretion results from Sermorelin administration.5 After sermorelin stimulates the release of GH from the pituitary gland, it increases synthesis of IGF-1 in the liver and peripheral tissues.5
Sermorelin acts on the growth hormone releasing hormone receptor (GHRHr) in the pituitary to regulate cellular activities. GHRHr is the natural receptor for the endogenous hormone, GHRH, and for sermorelin. This receptor regulates growth hormone release directly by stimulation and indirectly by a feedback relationships with somatostatin.6
Sermorelin is readily degraded after reaching the bloodstream, having a biological half-life of approximately 10-20 min.7 Due to the biological half-life and bioavailability of Sermorelin, administration for growth in childhood GHD must occur periodically several times a day as subcutaneous-injections.8 However, single daily dosing is sufficient to treat most cases of adult-onset GH insufficiency. Three (3) mcg/kg subcutaneous-injections of Sermorelin have been reported to simulate a naturally occurring GHRH mediated GH release responses.9
In addition to increasing production and secretion GHRH also affects sleep patterns by increasing the amount of slow wave sleep (SWS) while augmenting sleep-related GH secretion and reducing cortisol secretion.10
To exert all its beneficial effects, Sermorelin requires a functioning pituitary and a host of peripheral tissues.1112 This is due to the reliance on endogenous receptors controlling hormone secreting glands and tissues. More precisely, functioning growth hormone releasing hormone receptors (GHRHr) are required on somatotrophs in a functioning anterior pituitary.11
Mechanism of Action: Sermorelin essentially mimics the hypothalamic peptide, GHRH. Sermorelin acts directly on the pituitary stimulating the somatotroph cells ability to produce and secrete GH.13 Sermorelin increases proliferation of somatotroph cells during development.13 With the increase of serum GH, downstream effects occur. A notable hormone that is commonly used as a surrogate for growth hormone therapy, insulin like growth factor 1 (IGF-1), is known to increase with the administration of Sermorelin. IGF-I negatively regulates GHRH-mediated GH secretion.14
Sermorelin is able to influence the concert of hormonal signaling that effects the GH axis. GH secretion from the anterior pituitary is regulated by GHRH, somatostatin, and GH secretagogues. The positive and negative opposing regulation of growth hormone by GHRH and somatostatin creates a rhythmic-circadian GH secretion. GH asked by signaling target cells, most notably increasing the synthesis of IGF-1 in the liver and peripheral tissues.13
Sermorelin acts on the growth GHRHr in the pituitary to regulate cellular actives. GHRHr is the natural receptor for the endogenous hormone GHRH, a signaling hormone produced by the hypothalamus. This receptor among many other functions, controls growth hormone release, mainly by inhibition of somatostatin activity.15
Key warnings before taking this medicine: Tell your doctor your medical history, especially of: thyroid problems, brain disorders (e.g., lesions) and any allergies. Discuss the risks and benefits with your doctor with use in pregnant women. It is not known whether this drug passes into breast milk. Because of the potential risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.
How is it best taken? Inject this medication subcutaneously before bedtime, or as directed by your healthcare provider.
What do I do if I miss a dose? If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.
What are the precautions for taking this medicine? Tell your doctor of all prescription and nonprescription medication you may use, especially: corticosteroids and thyroid medications. This drug may affect the results of certain lab tests (e.g., inorganic phosphorus, alkaline phosphatase). Make sure laboratory personnel and your doctors know you use this drug. Do not start or stop any medicine without approval from your healthcare provider. Hypothyroidism: Untreated hypothyroidism can jeopardize the response to Sermorelin. Thyroid hormone determinations should be performed before the initiation and during therapy. Thyroid hormone replacement therapy should be initiated when indicated. Intracranial lesions: Patients with GH deficiency secondary to an intracranial lesion were not studied in clinical trials; Sermorelin treatment is not recommended in such patients. Obesity, hyperglycemia or hyperlipidemia: Subnormal GH responses have been seen in obesity and hyperglycemia, and in patients with elevated plasma fatty acids.
Pregnancy and Lactation: FDA pregnancy risk category C. Exercise caution during lactation; it is not known if this drug is excreted in breast milk. Laboratory Tests: Serum levels of inorganic phosphorus, alkaline phosphatase, GH and IGF-I may increase with therapeutic use. Corticosteroids: Glucocorticoids may inhibit the response to Sermorelin. Controlled studies did not indicate an interaction of Sermorelin with drugs commonly used in the treatment of routine pediatric problems/illnesses. However, formal drug interaction studies have not been conducted.
Who should not take this medicine? HGH is traditionally contraindicated in individuals with: Benign intracranial hypertension (BIH), critically ill persons (e.g., after complications following open heart or abdominal surgery, multiple trauma, acute respiratory failure or similar conditions), diabetic retinopathy, persons with evidence of tumor activity; in persons with tumors, anti-tumor therapy must be completed before initiating HGH therapy, persons with known hypersensitivity to HGH or to any of its excipients, women who are pregnant, planning to become pregnant, or lactating.
What are some possible side effects of this medicine? Call your doctor for medical advice if pain/swelling/redness occurs at the injection site (occurring in approximately 16% of patients). Other possible, but less common side effects of rhGH (not Sermorelin) are upper respiratory conditions, nerve sensitivity, insomnia, depression, nausea, hypothyroidism chest pain, gynecomastia, headache, flushing, dysphagia, dizziness, hyperactivity, somnolence, urticaria and sore bones. Call your health care provider immediately if you are experiencing trouble swallowing, vomiting, and tightness in the chest. Antibody formation to Sermorelin has been reported after chronic subcutaneous administration of large doses but their clinical significance is unknown. Antibodies do not appear to affect growth hormone release nor appear to be related to a specific adverse drug reaction profile. No generalized allergic reactions have been reported. A temporary allergic reaction described by severe redness, swelling and urticaria at the injection sites has been reported in one patient who developed antibodies. Additionally, its use may reduce insulin sensitivity, thereby raising blood sugar to levels which could be harmful to diabetes sufferers. It may also decrease triiodothyronine (T3) levels due to its tendency to reduce the bodily levels of sodium, potassium, and phosphorous.
How should I store this medicine? Keep this medicine in a refrigerator below 41°F (5°C). If precipitates start to form within the solution warm a cup of water to 90°C and place vial into the warm water until the precipitates go back into solution. Keep all medicine out of the reach of children. Throw away any unused medicine after the expiration date. Do not flush unused medications or pour down a sink or drain.
General Warnings: HGH is traditionally contraindicated in individuals with benign intracranial hypertension (BIH), critically ill persons (e.g., after complications following open heart or abdominal surgery, multiple trauma, acute respiratory failure or similar conditions), diabetic retinopathy, and persons with evidence of tumor activity. In persons with tumors, anti-tumor therapy must be completed before initiating HGH therapy. Persons with known hypersensitivity to HGH or to any of its excipients, women who are pregnant, planning to become pregnant, or lactating should not use this product.
- 1. Wehrenberg WB, Ling N. 1983. "In vivo biological potency of rat and human growth hormone-releasing factor and fragments of human growth hormone-releasing factor". Biochem Biophys Res Commun. 115 (2): 525–530.
- 2. Chen, R.G., et al., 1993. A comparative study of growth hormone (GH) and GH-releasing hormone (1-29)-NH2 for stimulation of growth in children with GH deficiency. Acta Paediatr Suppl, 388: p. 32-5; discussion 36.
- 3. Perez-Romero, A., et al., 1999. Effect of long-term GHRH and somatostatin administration on GH release and body weight in prepubertal female rats. J Physiol Biochem, 55(4): p. 315-24.
- 4. Tannenbaum, G.S. and Ling N. 1984. The interrelationship of growth hormone (GH)-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion. Endocrinology, 115(5): p. 1952-7.
- 5. a. b. Tauber, M.T., et al., 1993. Growth hormone (GH) profiles in response to continuous subcutaneous infusion of GH-releasing hormone(1-29)-NH2 in children with GH deficiency. Acta Paediatr Suppl, 388: p. 28-30; discussion 31.
- 6. Howard AD, Feighner SD, Cully DF et al. 1996, A Receptor in Pituitary and Hypothalamus That Functions in GH release. Science. Vol. 273, Issue 5277, pp. 974-977
- 7. Esposito, P., et al., 2003. PEGylation of growth hormone-releasing hormone (GRF) analogues. Adv Drug Deliv Rev, 55(10): p. 1279-91.
- 8. Kirk JM, Trainer PJ, Majrowski WH, Murphy J, Savage MO, Besser GM. 1994. Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity. Clin Endocrinol (Oxf). 41(4):487-93.
- 9. Aitman, T.J., et al., 1989. Bioactivity of growth hormone releasing hormone (1-29) analogues after SC injection in man. Peptides, 10(1): p. 1-4.
- 10. Steiger, A., et al., 1994. Growth hormone-releasing hormone (GHRH)-induced effects on sleep EEG and nocturnal secretion of growth hormone, cortisol and ACTH in patients with major depression. J Psychiatr Res, 28(3): p. 225-38.
- 11. a. b. Mayo, K.E., et al., 1995. Growth hormone-releasing hormone: synthesis and signaling. Recent Prog Horm Res, 50: p. 35-73.
- 12. Ceda, G.P., et al. 1987. The growth hormone (GH)-releasing hormone (GHRH)-GH-somatomedin axis: evidence for rapid inhibition of GHRH-elicited GH release by insulin-like growth factors I and II. Endocrinology, 120(4): p. 1658-62.
- 13. a. b. c. Mayo, K.E., et al., Growth hormone-releasing hormone: synthesis and signaling. Recent Prog Horm Res, 1995. 50: p. 35-73.
- 14. Ceda, G.P., et al., The growth hormone (GH)-releasing hormone (GHRH)-GH-somatomedin axis: evidence for rapid inhibition of GHRH-elicited GH release by insulin-like growth factors I and II. Endocrinology, 1987. 120(4): p. 1658-62.
- 15. Tannenbaum, G.S. and N. Ling, The interrelationship of growth hormone (GH)-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion. Endocrinology, 1984. 115(5): p. 1952-7.
- 16. Prakash, A. and K.L. Goa, Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs, 1999. 12(2): p. 139-57.
- 17. Walker, R.F., Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? Clin Interv Aging, 2006. 1(4): p. 307-8.