Tesamorelin

Tesamorelin Peptide

Tesamorelin is a highly specialized, synthetic Growth Hormone-Releasing Hormone (GHRH) analog engineered for enhanced biostability and sustained biological effect. It functions by potent and selective binding to human GHRH receptors found in the anterior pituitary gland, mimicking the action of endogenous GHRH. Clinical investigations have demonstrated Tesamorelin's ability to significantly increase the systemic concentration of Insulin-like Growth Factor 1 (IGF-1), with studies showing an average increase of 181 micrograms per liter in men.

The research profile of Tesamorelin suggests broad metabolic and structural potential beyond primary growth hormone (GH) stimulation, including:

• Metabolic Regulation: Observed reductions in triglyceride and systemic C-reactive protein (CRP) levels, indicating potential anti-inflammatory and lipid-regulating effects.
• Vascular and Body Composition: Demonstrated efficacy in reducing visceral adipose tissue (VAT) and decreasing carotid intima-media thickness (cIMT) in research models.
• Neurological Research: Exploration of its function as a nootropic agent, supporting cognitive health research in aging subjects and in models of mild cognitive impairment, particularly those associated with elevated risks for conditions like Alzheimer's disease.

Importantly, the mechanism of action for Tesamorelin appears to be highly targeted, with no significant alterations reported in the regulatory feedback loops or circulating levels of other critical pituitary hormones.

Tesamorelin Peptide Overview

Mechanism of Action

Tesamorelin initiates its activity through direct agonism of the GHRH receptors located on the somatotroph cells within the anterior pituitary gland. This targeted activation enhances the natural, pulsatile secretion of Growth Hormone (GH). GH subsequently triggers the liver to produce and secrete Insulin-like Growth Factor 1 (IGF-1), which serves as the principal anabolic mediator for GH, promoting tissue regeneration and inhibiting cellular apoptosis. Furthermore, GH exhibits powerful lipolytic effects, specifically mobilizing and breaking down stored fat, particularly in the abdominal and visceral compartments.

The proposed signaling pathway involves Tesamorelin binding to the GHRH receptor, inducing a conformational change that activates the intracellular machinery:

1. Enzyme Activation: Tesamorelin binding is hypothesized to activate adenylate cyclase, catalyzing the conversion of ATP into the key secondary messenger cyclic AMP (cAMP).
2. Signal Propagation: The elevated levels of intracellular cAMP stimulate Protein Kinase A (PKA), which then initiates a cascade of phosphorylation events.

This combined GHRH receptor and cAMP-PKA signaling is understood to significantly boost the synthesis and release of GH. Research data supports this, showing approximately a 69% increase in total GH exposure (AUC) and a 55% rise in mean pulse area, while preserving the endogenous pulse frequency. This mechanism results in a notable increase in systemic IGF-1 levels, reported at roughly 122%.

Product Structure

Tesamorelin is a synthetic 44-amino acid peptide derived from human GHRH, incorporating two strategic chemical modifications to improve its pharmacokinetic profile and stability against proteases.

• C-terminus Modification: The molecule is modified with a trans-3-hexenoyl group at the C-terminus. This structural change provides significant protection against rapid enzymatic breakdown within biological systems.
• N-terminus Modification: An acetyl (CH3CO) group is attached to the N-terminus, which is critical for enhancing both the peptide’s stability and its biological activity.

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

Tesamorelin Research

Extensive clinical and preclinical studies have detailed the multifaceted effects of Tesamorelin, particularly focusing on metabolic and body composition changes.

Research Focus

Study Design and Context

Key Research Findings

Visceral Adipose Tissue (VAT) Reduction

Pooled analysis of two Phase III clinical trials over a 26-week period involving subjects with HIV-associated lipodystrophy.

Achieved a significant reduction in VAT, with a minimum decrease of 15.4% by week 26. Also demonstrated simultaneous reductions in circulating triglyceride and cholesterol levels compared to placebo.

Non-Alcoholic Fatty Liver Disease (NAFLD) Markers

12-month clinical investigation in 61 HIV-positive participants with documented elevated hepatic fat fraction (HFF).

35% of Tesamorelin-treated subjects showed a measurable HFF reduction of less than 5%, a statistically significant outcome compared to only 4% of the placebo group. No significant impact on systemic glucose levels was noted.

Musculoskeletal Composition

Evaluation using high-resolution Computed Tomography (CT) imaging in adults with HIV to analyze muscle structure.

Showed statistically significant alterations in muscle quality and composition in several groups (e.g., rectus abdominis, psoas major, paraspinal muscles), including increases in muscle density and size or a reduction in intramuscular fat content.

Cognitive Function (Ongoing Trial)

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

Study is focused on the change in the Global Deficit Score as the primary endpoint at 6 and 12 months. Final results are currently awaited.

Insulin Sensitivity

12-week randomized clinical trial involving 53 participants with Type 1 Diabetes, using varying doses of the peptide.

Found no statistically significant difference in fasting glucose, HbA1c levels, or required insulin dosage between the treatment and placebo groups, suggesting no major effect on insulin sensitivity under these 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 shipped in a highly stable lyophilized (freeze-dried) form. This process, known as cryodesiccation, involves freezing the peptide and removing water via sublimation, resulting in a crystalline powder. The lyophilized state ensures exceptional stability during shipping, typically lasting approximately three to four months.

Proper handling and storage are crucial to maintain peptide integrity:

• Upon Receipt: Peptides must be stored in a cool, dark place.
• Short-Term Storage (Days to Months): For prompt use, refrigeration below 4 degrees C (39 degrees F) is appropriate. Lyophilized peptides have shown stability at room temperature for several weeks, which can suffice for brief storage.
• Long-Term Storage (Months to Years): For maximizing the peptide's shelf life over extended periods, storage in a freezer at -80 degrees C (-112 degrees F) is the recommended best practice, preserving structural integrity.

Once the peptide is reconstituted with bacteriostatic water, the resulting solution must be stored under refrigeration. In solution, the peptide typically retains stability for up to 30 days.

Best Practices for Storing Peptides

Strict adherence to storage protocols is vital for experimental consistency and data reliability. Correct procedures prevent degradation from heat, light, oxidation, and moisture.

1. Minimize Temperature Stress: Avoid repeated freeze-thaw cycles as they rapidly accelerate degradation. Do not use frost-free freezers for long-term storage, as their automated defrost cycles cause destabilizing temperature fluctuations.
2. Aliquotting: To prevent unnecessary exposure and handling of the entire stock, it is strongly advised to divide the total peptide into smaller, single-use aliquots immediately upon receipt.

Preventing Oxidation and Moisture Contamination

Exposure to air and moisture can compromise peptide stability, particularly for peptides containing residues like cysteine (C), methionine (M), or tryptophan (W), which are prone to oxidation.

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

Storing Peptides in Solution

Peptides dissolved in solution are significantly more prone to bacterial degradation and have a much shorter shelf life than the lyophilized form. Peptides containing residues such as cysteine (Cys), methionine (Met), tryptophan (Trp), aspartic acid (Asp), glutamine (Gln), or N-terminal glutamic acid (Glu) are less stable in solution.

• Optimal Conditions: If solution storage is required, use sterile buffers with a value between 5 and 6. Aliquotting the solution is also recommended to reduce freeze-thaw cycles.
• Stability: Peptide solutions stored under refrigeration at 4 degrees C (39 degrees F) generally remain stable for up to 30 days. Peptides with known instability should be kept frozen when not in 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 peptides in their lyophilized form for long-term preservation.
• Aliquot peptides to limit handling and maintain integrity.