Tesamorelin

Tesamorelin Peptide

Tesamorelin is a structurally optimized, synthetic analog of Growth Hormone-Releasing Hormone (GHRH), engineered to enhance its half-life and biological effectiveness. It functions by selectively and potently binding to the GHRH receptors found in the anterior pituitary gland, thereby amplifying the body’s natural GH signaling pathway. The peptide is clinically documented to produce a significant increase in circulating Insulin-like Growth Factor 1 (IGF-1), with studies reporting an average elevation of 181 micrograms per liter in research subjects.

The research applications for Tesamorelin are extensive, focusing on its potential to influence:

• Metabolic Syndrome Markers: Demonstrated reductions in visceral adipose tissue (VAT), a reduction in triglyceride levels, and decreased inflammatory markers, including C-reactive protein (CRP).
• Vascular Health: Observed potential for reducing carotid intima-media thickness (cIMT) in research models.
• Neurocognitive Research: Its function as a nootropic agent is being investigated to support cognitive function in older adults and individuals with mild cognitive impairment, including those at an elevated risk for neurodegenerative diseases.

Tesamorelin's mechanism is highly selective, with studies showing no significant disruption to the homeostatic control or secretion of other major pituitary hormones.

Tesamorelin Peptide Overview

Mechanism of Action

Tesamorelin's action is localized to the anterior pituitary gland, where it binds specifically to the GHRH receptors on somatotroph cells. This binding serves as a powerful stimulus, enhancing the endogenous, pulsatile release of Growth Hormone (GH). GH then acts indirectly, primarily on the liver, to induce the production and release of Insulin-like Growth Factor 1 (IGF-1). IGF-1 is the crucial messenger for GH's anabolic effects, facilitating tissue maintenance and synthesis. Concurrently, GH possesses potent lipolytic properties, contributing to the mobilization and breakdown of stored fat, notably targeting visceral fat accumulation.

The key intracellular events following GHRH receptor binding are hypothesized to include:

1. Cyclic AMP Synthesis: Activation of the receptor stimulates the enzyme adenylate cyclase, which converts ATP into the intracellular signaling molecule cyclic AMP (cAMP).
2. Kinase Signaling: The subsequent increase in cAMP concentration activates Protein Kinase A (PKA), thereby initiating the phosphorylation cascade necessary for GH synthesis and secretion.

This synergistic pathway leads to significantly enhanced GH activity. Research indicates this mechanism is responsible for an approximately 69% increase in total GH exposure (AUC) and a 55% increase in mean pulse area, while preserving the natural rhythm of GH release. The net result is a robust increase in systemic IGF-1 levels, reported to be around 122%.

Product Structure

Tesamorelin is a synthetic 44-amino acid peptide, engineered with key modifications to confer exceptional stability and resistance to enzymatic degradation (proteolysis) compared to native GHRH. These structural enhancements are located at both the N- and C-terminal ends of the molecule:

• C-terminus Modification: The peptide incorporates a trans-3-hexenoyl group at the C-terminus. This specific fatty acid modification is essential for protecting the peptide from rapid enzymatic breakdown in biological systems.
• N-terminus Modification: The molecule is capped with an acetyl (CH3CO) group at the N-terminus, which is crucial for maximizing its stability and maintaining sustained biological activity.

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

Tesamorelin Research

Tesamorelin has been extensively studied in clinical settings, providing detailed insights into its impact on body composition and metabolic parameters in various research models.

Research Focus

Study Design and Context

Key Research Findings

Visceral Adipose Tissue (VAT) Reduction

Pooled analysis of two Phase III trials (26-week core phase) in individuals with HIV-associated lipodystrophy.

Led to a significant reduction in VAT, with a minimum decrease of 15.4%. Corresponding reductions were noted in circulating triglyceride and cholesterol levels compared to placebo.

Hepatic Fat Fraction (HFF) / NAFLD Research

12-month clinical investigation involving 61 HIV-positive participants with elevated HFF (a measurement of liver fat).

35% of the Tesamorelin-treated group showed a measurable HFF reduction of less than 5%, a statistically superior result compared to the 4% observed in the placebo group. No notable changes in blood glucose homeostasis were recorded.

Muscle Structure and Quality

Evaluation using Computed Tomography (CT) imaging to assess changes in skeletal muscle in adults with HIV.

Statistically significant improvements in muscle quality were observed in specific groups (e.g., rectus abdominis, psoas major, paraspinal muscles), including increases in muscle density and size or reductions in intramuscular fat content compared to controls.

Cognitive Function (Ongoing Trial)

Phase II clinical investigation (100 immunodeficient subjects over 40) examining neurological outcomes over a 12-month period.

The primary endpoint being evaluated is the change in the Global Deficit Score at 6 and 12 months. Final data are pending publication.

Insulin Sensitivity (Type 1 Diabetes)

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

No statistically significant differences were observed between the treatment and placebo groups for changes in fasting glucose, HbA1c levels, or required daily insulin dosage, suggesting a neutral effect on insulin sensitivity under these conditions.

Article Author

Scientific Journal Author

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 delivered as a lyophilized (freeze-dried) powder, which is the optimal state for long-term preservation. The lyophilization process (cryodesiccation) removes water by sublimation, creating a highly stable crystalline structure that retains integrity during shipping for approximately three to four months.

Storage guidelines for maintaining peptide quality:

• Upon Receipt: Peptides must be stored in a cool, dry, and dark environment.
• Short-Term Storage (Days to Months): For prompt use, refrigeration at temperatures below 4 degrees C (39 degrees F) is appropriate. The lyophilized form maintains stability at room temperature for several weeks, acceptable for minimal storage duration.
• Long-Term Storage (Months to Years): For maximum stability and prolonged preservation, storage in a freezer at -80 degrees C (-112 degrees F) is the industry best practice.

Once the peptide is reconstituted using bacteriostatic water, the solution requires refrigeration and typically maintains its stability for a period of up to 30 days.

Best Practices for Storing Peptides

Strict adherence to storage protocols is fundamental for ensuring the reliability and accuracy of experimental results. Proper procedures minimize degradation from thermal cycling, oxidation, and contamination.

1. Avoid Temperature Stress: Minimize repeated freeze-thaw cycles as they rapidly degrade peptide integrity. Avoid frost-free freezers for long-term storage due to their temperature fluctuations during defrosting cycles.
2. Aliquoting: To prevent the entire stock from repeated handling and exposure, it is highly recommended to divide the total peptide into smaller, single-use aliquots immediately upon receipt.

Preventing Oxidation and Moisture Contamination

Exposure to moisture and air (oxygen) significantly degrades peptide stability. Peptides containing residues like cysteine (C), methionine (M), or tryptophan (W) are especially susceptible to oxidation.

• Moisture Control: Always allow the peptide vial to reach room temperature before opening when removing it from cold storage. This prevents atmospheric moisture from condensing inside the vial.
• Oxidation Control: Keep the container sealed whenever possible. After dispensing, promptly reseal the vial. Storing the remaining product under a dry, inert gas atmosphere (e.g., nitrogen or argon) can provide an added layer of protection against oxidation.

Storing Peptides in Solution

Peptides stored in solution exhibit a significantly shorter shelf life and are more susceptible to chemical and microbial degradation than the lyophilized powder. Peptides containing residues such as cysteine (Cys), methionine (Met), tryptophan (Trp), aspartic acid (Asp), glutamine (Gln), or N-terminal glutamic acid (Glu) are known to degrade faster when dissolved.

• Optimal Buffer: If solution storage is unavoidable, use sterile buffers with a value between 5 and 6. The solution should also be aliquoted to minimize freeze-thaw events.
• Solution Stability: Most solutions, when refrigerated at 4 degrees C (39 degrees F), remain stable for up to 30 days. Highly sensitive peptides should be kept frozen if not intended for immediate use.

Peptide Storage Guidelines: General Tips

• Store peptides in a cold, dry, and dark environment.
• Avoid repeated freeze-thaw cycles.
• Minimize air exposure to reduce the risk of oxidation.
• Protect from light.
• Store in lyophilized form for long-term preservation.
• Aliquot peptides to limit stock handling.