Tesamorelin

Tesamorelin

Tesamorelin is a highly specialized synthetic analog of Growth Hormone-Releasing Hormone (GHRH), purposefully modified to exhibit superior stability and prolonged biological activity compared to the naturally occurring hormone. It functions as a powerful agonist by activating and binding to human GHRH receptors located on the somatotroph cells of the anterior pituitary gland with comparable efficacy to the endogenous peptide. Clinical investigations have consistently demonstrated Tesamorelin's capacity to induce a significant elevation in circulating levels of Insulin-like Growth Factor 1 (IGF-1), with studies in men showing an average increase of 181 micrograms per liter.

Tesamorelin's utility in research extends beyond its primary role in stimulating growth hormone release. Potential benefits observed in various research contexts include:

• Cardiometabolic Markers: Reduction of visceral adipose tissue (VAT), lowering of triglyceride levels, and decrease in circulating C-reactive protein (CRP), a marker of inflammation.
• Vascular Health: Attenuation of carotid intima-media thickness (cIMT).
• Neurocognitive Function: Exploration of nootropic (cognitive-enhancing) properties, particularly in aged subjects and individuals with mild cognitive impairment, including those with elevated risk factors for Alzheimer's disease.

A key advantage of Tesamorelin noted in research is its mechanism, which does not appear to significantly disrupt the normal regulatory feedback loops or alter the secretion of other critical pituitary hormones.

Tesamorelin Peptide Overview

Mechanism of Action

The mechanism of Tesamorelin centers on the hypothalamic-pituitary-somatotroph axis. The peptide is believed to stimulate the physiological cascade by selectively binding to and activating GHRH receptors situated on the membranes of somatotroph cells in the anterior pituitary gland. This targeted action enhances the endogenous, pulsatile secretion of Growth Hormone (GH), which in turn stimulates the hepatic production and systemic release of IGF-1. IGF-1 is recognized as the principal mediator of GH's anabolic effects, critical for promoting tissue synthesis and inhibiting apoptosis (programmed cell death). GH itself is a potent lipolytic agent, facilitating the breakdown and mobilization of fat, especially in problematic areas like abdominal and visceral fat stores.

The activation of the GHRH receptor by Tesamorelin is hypothesized to induce a conformational change that triggers a complex intracellular signaling cascade. This cascade is thought to involve:

1. Cyclic AMP (cAMP) Generation: Activation of the enzyme adenylate cyclase leads to the conversion of adenosine triphosphate (ATP) into the secondary messenger cyclic AMP.
2. Protein Kinase A (PKA) Activation: Increased intracellular cAMP levels subsequently stimulate Protein Kinase A (PKA), initiating the phosphorylation of various downstream targets.

The synergistic activation of GHRH receptors and the cAMP-PKA pathway significantly augments the exocytosis and subsequent release of GH from the somatotroph cells. Pharmacokinetic studies have documented a robust physiological response, including an approximate 69% increase in total systemic Growth Hormone exposure (Area Under the Curve, or AUC) and a roughly 55% rise in the mean pulse area, while maintaining the natural frequency and amplitude of GH pulses. This enhanced GH action correlates with a substantial increase in circulating IGF-1 levels, reported at approximately 122%.

Product Structure

Tesamorelin is a forty-four amino acid peptide derived from GHRH, containing specific structural modifications designed to confer superior stability and resistance to enzymatic degradation (proteolysis) compared to native GHRH. These modifications occur at both the N-terminal and C-terminal segments of the molecule.

• C-terminus Modification: The peptide incorporates a trans-3-hexenoyl group at the C-terminus. This specific fatty acid modification is known to provide protection against common enzymatic cleavage.
• N-terminus Modification: The N-terminus is capped with an acetyl (CH3CO) group. This alteration further contributes to enhanced stability and ensures the maintenance of high biological activity.

The precise chemical designation for Tesamorelin is: N-(trans-3-hexenoyl)-[Tyr 1]hGHRF(1-44)NH2 acetate.

Tesamorelin Research

Tesamorelin has been the subject of extensive peer-reviewed clinical research exploring its potential therapeutic applications, primarily in the context of metabolic and body composition disorders. A summary of key research findings is provided below:

Research Focus

Study Design and Context

Key Research Findings

Visceral Adipose Tissue (VAT) & Lipodystrophy

Pooled analysis of two Phase III trials (806 participants) over 26 weeks in individuals with HIV-associated lipodystrophy.

Demonstrated a significant reduction in VAT, achieving a decrease of at least 15.4% by week 26. Also resulted in notable reductions in both circulating triglyceride and cholesterol levels compared to placebo.

Hepatic Fat Fraction (HFF) / NAFLD

12-month clinical trial involving 61 HIV-positive participants with elevated HFF (a marker for non-alcoholic fatty liver disease).

35% of participants receiving Tesamorelin experienced a reduction in HFF of less than 5%, a significant improvement over the 4% observed in the placebo group. No material changes in glucose homeostasis were reported.

Skeletal Muscle Composition

Evaluation using Computed Tomography (CT) imaging to assess structural integrity and fat content in adults with HIV.

Statistically significant changes were observed in key muscle groups (e.g., rectus abdominis, psoas major, paraspinal muscles), including increases in muscle size and density or decreases in intramuscular fat content compared to control groups.

Cognition in Mild Cognitive Impairment

Ongoing Phase II trial (100 immunodeficient subjects over age 40) investigating neurological outcomes over a 12-month period.

The study is actively evaluating the change in the Global Deficit Score at 6 and 12 months as the primary outcome measure. Final data are pending publication.

Insulin Sensitivity (Type 1 Diabetes)

12-week randomized trial with 53 participants with Type 1 Diabetes.

No significant differences were observed between the Tesamorelin-treated and placebo groups regarding changes in fasting glucose, levels, or required insulin dosage, indicating no major impact on insulin sensitivity under the study conditions.

Reference Citations

Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Tesamorelin. [Updated 2018 Oct 20]. https://www.ncbi.nlm.nih.gov/books/NBK548730/

Spooner, L. M., & Olin, J. L. (2012). Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy. The Annals of pharmacotherapy, 46(2), 240-247. https://doi.org/10.1345/aph.10629

Stanley TL, Chen CY, Branch KL, Makimura H, Grinspoon SK. Effects of a growth hormone-releasing hormone analog on endogenous GH pulsatility and insulin sensitivity in healthy men. J Clin Endocrinol Metab. 2011 Jan;96(1):150-8. doi: 10.1210/jc.2010-1587. Epub 2010 Oct 13. PMID: 20943777; PMCID: PMC3038486. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038486/

Ferdinandi ES, Brazeau P, High K, Procter B, Fennell S, Dubreuil P. Non-clinical pharmacology and safety evaluation of TH9507, a hu- man growth hormone-releasing factor analogue. Basic Clin Pharmacol Toxicol. 2007 Jan;100(1):49-58. doi: 10.1111/j.1742- 7843.2007.00008.x. PMID: 17214611. https://pubmed.ncbi.nlm.nih.gov/17214611/

Stanley, T. L., Fourman, L. T., Feldpausch, M. N., Purdy, J., Zheng, I., Pan, C. S., Aepfelbacher, J., Buckless, C., Tsao, A., Kellogg, A., Branch, K., Lee, H., Liu, C. Y., Corey, K. E., Chung, R. T., Torriani, M., Kleiner, D. E., Hadigan, C. M., & Grinspoon, S. K. (2019). Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. The lancet. HIV, 6(12), e821- e830. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981288/

Falutz J, Mamputu JC, Potvin D, Moyle G, Soulban G, Loughrey H, Marsolais C, Turner R, Grinspoon S. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010 Sep;95(9):4291-304. doi: 10.1210/jc.2010-0490. Epub 2010 Jun 16. PMID: 20554713. https://pubmed.ncbi.nlm.nih.gov/20554713/

Tesamorelin Effects on Liver Fat and Histology in HIV. https://clinicaltrials.gov/ct2/show/NCT02196831

Phase II Trial of Tesamorelin for Cognition in Aging HIV-Infected Persons. https://clinicaltrials.gov/ct2/show/record/NCT02572323

Clemmons, D. R., Miller, S., & Mamputu, J. C. (2017). Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analogue, in patients with type 2 diabetes: A randomized, placebo-controlled trial. PloS one, 12(6), e0179538. https://www.ncbi.nlm.nih. gov/pmc/articles/PMC5472315/

Adrian S, Scherzinger A, Sanyal A, Lake JE, Falutz J, Dubé MP, Stanley T, Grinspoon S, Mamputu JC, Marsolais C, Brown TT, Erlandson KM. The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV. J Frailty Aging. 2019;8(3):154-159. doi: 10.14283/jfa.2018.45. PMID: 31237318; PMCID: PMC6766405. https://www.ncbi.nlm.nih.gov/pmc/ articles/PMC6766405/

Sivakumar T, Mechanic O, Fehmie DA, Paul B. Growth hormone axis treatments for HIV-associated lipodystrophy: a systematic review of placebo-controlled trials. 12. HIV Med. 2011 Sep;12(8):453-62. doi: 10.1111/j.1468-1293.2010.00906.x. Epub 2011 Jan 25. PMID: 21265979.

ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.

The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.

Storage

Storage Instructions

Tesamorelin is provided in a lyophilized (freeze-dried) format. This specialized dehydration process, also known as cryodesiccation, is designed to maximize the peptide's stability, typically ensuring preservation during transport for approximately three to four months. Lyophilization involves freezing the peptide and then reducing the pressure, allowing the frozen water to sublimate directly into a gas. The resulting stable, white crystalline powder can be maintained at ambient temperature until the point of reconstitution.

Upon receipt, peptides should always be kept cool and protected from light to prevent degradation.

• Short-Term Storage (Days to Months): For prompt use, refrigeration at temperatures below 4 degrees C (39 degrees F) is suitable. Lyophilized peptides generally retain stability at room temperature for several weeks, which is acceptable for very brief storage periods prior to use.
• Long-Term Storage (Months to Years): For prolonged preservation, such as several months to years, optimal stability is achieved by storing the peptide in a freezer at -80 degrees C (-112 degrees F). This ultra-low temperature helps preserve the peptide's structural integrity over extended periods.

Once the peptide is reconstituted with bacteriostatic water, the solution must be stored in a refrigerator to maintain its potency and will typically remain stable for a period of up to 30 days.

Best Practices for Storing Peptides

Implementing correct storage procedures is essential for guaranteeing the accuracy and reproducibility of laboratory results. Proper handling helps mitigate the risk of contamination, oxidation, and structural degradation, thereby maximizing the peptide's effective lifespan.

1. Minimize Freeze-Thaw Cycles: Repeated fluctuations in temperature drastically accelerate peptide degradation. It is crucial to avoid frost-free freezers, as they undergo regular temperature variations during their defrosting cycles, which can compromise stability.
2. Aliquot for Experimental Use: To prevent repeated exposure to air and temperature stress, a practical strategy is to divide the total peptide quantity into smaller, single-use aliquots immediately upon receipt. This method prevents the entire batch from being subjected to multiple freeze-thaw cycles or handling.

Preventing Oxidation and Moisture Contamination

Protecting the peptide from air and moisture is paramount for maintaining its integrity. Peptides containing the residues cysteine (C), methionine (M), or tryptophan (W) are particularly susceptible to air oxidation and require meticulous handling.

• Moisture Control: Condensation (moisture contamination) is a significant risk when retrieving cold peptides from the freezer. Always allow the vial to fully acclimate to room temperature before opening it to prevent water vapor from condensing on the peptide or inside the container.
• Oxidation Control: The peptide container should remain sealed as much as possible. After dispensing the required amount, the container should be promptly resealed. For enhanced long-term stability, storing the remaining peptide under a dry, inert gas atmosphere (such as argon or nitrogen) can further minimize exposure to oxygen.

Storing Peptides in Solution

Peptides stored in solution have a substantially reduced shelf life and are more vulnerable to chemical and bacterial degradation compared to their lyophilized form. Peptides containing the residues cysteine (Cys), methionine (Met), tryptophan (Trp), aspartic acid (Asp), glutamine (Gln), or N-terminal glutamic acid (Glu) are noted to degrade more rapidly when dissolved.

• Recommended Buffer: If preparing a solution is necessary, it is best to use sterile buffers with a slightly acidic pH range, ideally between 5 and 6.
• Solution Stability: Under refrigerated conditions at 4 degrees C (39 degrees F), most peptide solutions are stable for a period of up to 30 days. However, less stable peptides should be frozen if they are not intended for immediate use to best preserve their structural integrity.

Peptide Storage Containers

Containers used for peptide storage must be chemically resistant, durable, and clean. The container size should be appropriate for the peptide volume to minimize unnecessary air space.

• Material Selection: Both glass and plastic vials (e.g., polystyrene or polypropylene) are commonly used. High-quality glass vials offer superior characteristics, including chemical inertness and clarity, making them generally the best choice for long-term storage. Polypropylene vials provide better chemical resistance, while polystyrene is clearer but less chemically inert.
• Practicality: While peptides are often shipped in plastic to mitigate breakage risk, they can be safely transferred to glass vials for optimized long-term storage, depending on experimental requirements.

Peptide Storage Guidelines: General Tips

Adherence to these key practices will help maintain the highest possible peptide stability and integrity:

• Store peptides in a cold, dry, and dark environment.
• Avoid repeated freeze-thaw cycles entirely.
• Minimize air exposure to prevent chemical oxidation.
• Protect peptides from light exposure to prevent photo-induced degradation.
• Do not store peptides in solution long-term; utilize the lyophilized form whenever feasible.
• Aliquot peptides based on planned experimental use to limit unnecessary handling and exposure of the entire stock.