Tesamorelin

Tesamorelin Peptide

Tesamorelin is a chemically engineered, synthetic Growth Hormone-Releasing Hormone (GHRH) analog recognized for its extended half-life and potent biological activity. It operates via the selective activation and binding to human GHRH receptors found within the anterior pituitary gland, effectively mimicking the body's natural signaling molecule. Research has robustly demonstrated Tesamorelin's capacity to elevate circulating levels of Insulin-like Growth Factor 1 (IGF-1), with quantitative studies reporting an average increase of 181 micrograms per liter in male subjects.

Tesamorelin's research applications extend into several critical areas, showcasing its potential for:

• Cardiovascular and Metabolic Health: Evidence suggests its role in reducing carotid intima-media thickness (cIMT), decreasing visceral adipose tissue (VAT), and lowering inflammatory markers like C-reactive protein (CRP), alongside significant reductions in triglyceride levels.
• Neurological Research: Preliminary research explores its nootropic (cognitive-enhancing) potential, particularly in models involving older adults and those with mild cognitive impairment, including populations at high risk for Alzheimer’s disease.

The peptide is noted for its high specificity, as research indicates it does not appear to significantly interfere with the production or regulatory mechanisms of other hormones secreted by the pituitary gland.

Tesamorelin Peptide Overview

Mechanism of Action

Tesamorelin strategically targets the somatotroph cells of the anterior pituitary gland, which are responsible for producing and releasing Growth Hormone (GH). By binding to and activating the GHRH receptors on these cells, Tesamorelin initiates a complex signaling cascade that enhances the endogenous, pulsatile secretion of GH. The released GH then acts on peripheral tissues, primarily the liver, to stimulate the release of IGF-1. IGF-1 is the crucial downstream factor that mediates the anabolic effects of GH, supporting tissue growth and preventing cellular breakdown. GH itself contributes significantly through its lipolytic properties, promoting the breakdown of fat, especially visceral and abdominal fat stores.

The intracellular signaling events are understood to proceed as follows:

1. Receptor Activation and Enzyme Cascade: Binding of Tesamorelin is hypothesized to activate adenylate cyclase, leading to the conversion of ATP into the messenger molecule cyclic AMP (cAMP).
2. Kinase Stimulation: The elevated concentration of intracellular cAMP subsequently activates Protein Kinase A (PKA), which propagates the signal through phosphorylation.

This mechanism results in a notable enhancement of GH secretion. Quantitative studies have shown that Tesamorelin increases total systemic GH exposure (AUC) by approximately 69% and raises the mean pulse area by about 55%, without altering the inherent frequency or amplitude of the GH release pulses. This enhanced GH activity is directly reflected in the reported increase of circulating IGF-1 levels by approximately 122%.

Product Structure

Tesamorelin is a synthetic peptide containing 44 amino acids, expertly modified at both terminal ends to dramatically improve its in vivo stability and resistance to enzymatic degradation.

• C-terminus Modification: The molecule includes a stabilizing trans-3-hexenoyl group at the C-terminus, which protects the peptide from rapid breakdown by circulating enzymes.
• N-terminus Modification: An acetyl (CH3CO) group is incorporated at the N-terminus, a modification known to be instrumental in increasing the peptide's stability and sustained biological potency.

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

Tesamorelin Research

Tesamorelin has been the focus of multiple controlled clinical trials, yielding substantial data concerning its impact on body composition and metabolic parameters, particularly in challenging 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 subjects with HIV-associated lipodystrophy.

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

Hepatic Fat Fraction (HFF) / NAFLD Research

12-month study involving 61 HIV-positive participants diagnosed with elevated HFF (a key measure of fat in the liver).

35% of the group treated with Tesamorelin demonstrated a measurable reduction in HFF of less than 5%, markedly superior to the 4% observed in the placebo group. The treatment did not produce any significant changes in blood glucose levels.

Muscle Structure and Quality

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

Statistically significant improvements in several muscle groups (e.g., rectus abdominis, psoas major, paraspinal muscles) were recorded, including increases in muscle density and size or reductions in the content of intramuscular fat compared to control.

Cognitive Function (Ongoing Trial)

Phase II clinical investigation (100 immunodeficient subjects over 40) focusing on changes in neurological outcomes over 12 months.

The trial is designed to evaluate changes in the Global Deficit Score at 6 and 12 months. Final data collection and analysis are ongoing.

Insulin Sensitivity (Type 1 Diabetes)

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

No statistically significant differences were detected between the treatment and placebo groups concerning changes in fasting glucose, HbA1c levels, or daily insulin requirements, suggesting a neutral impact 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 supplied as a lyophilized (freeze-dried) powder, which is the most stable form for transport and storage. The lyophilization process, or cryodesiccation, involves the removal of water through sublimation, resulting in a crystalline structure that remains stable for approximately three to four months during shipping.

Critical storage considerations:

• Upon Receipt: The peptide must be stored in a cool, dry, and dark place.
• Short-Term Storage (Days to Months): For quick usage, refrigeration below 4 degrees C (39 degrees F) is adequate. The lyophilized form demonstrates stability at room temperature for several weeks, which is acceptable for minimal storage duration.
• Long-Term Storage (Months to Years): To ensure maximum structural integrity and stability over extended periods, the recommended best practice is freezing at -80 degrees C (-112 degrees F).

Once the peptide is reconstituted using bacteriostatic water, the resulting solution must be kept in the refrigerator. The stability of the solution is typically maintained for up to 30 days.

Best Practices for Storing Peptides

Proper storage is indispensable for guaranteeing the reproducibility and accuracy of experimental data. Following these guidelines helps protect the peptide from degradation caused by temperature variation, oxidation, and microbial growth.

1. Avoid Temperature Cycling: Minimize freeze-thaw cycles as much as possible, as repeated temperature changes dramatically accelerate degradation. For long-term preservation, avoid frost-free freezers due to the destabilizing temperature fluctuations during their automated defrost cycles.
2. Aliquoting: To prevent the entire batch from repeated handling and environmental exposure, it is best practice to divide the total peptide into smaller, predetermined aliquots immediately upon receipt, with each aliquot reserved for a single experimental use.

Preventing Oxidation and Moisture Contamination

Exposure to air (oxygen) and moisture is a major source of instability. Peptides containing cysteine (C), methionine (M), or tryptophan (W) are especially prone to oxidation and require rigorous protective measures.

• Moisture Control: When removing a peptide from cold storage, always allow the vial to reach room temperature before opening. This prevents moisture from the surrounding air from condensing inside the vial.
• Oxidation Control: Keep the vial sealed whenever possible. After dispensing, immediately reseal the container. Storing the remaining peptide under a dry, inert gas atmosphere (such as nitrogen or argon) can be implemented for superior protection against air oxidation.

Storing Peptides in Solution

Peptides stored in solution are significantly more susceptible to degradation (hydrolysis and oxidation) and bacterial contamination, resulting in a much shorter shelf life than the lyophilized powder. Less stable residues in solution include cysteine (Cys), methionine (Met), tryptophan (Trp), aspartic acid (Asp), glutamine (Gln), or N-terminal glutamic acid (Glu).

• Optimal Conditions: If solution storage is unavoidable, utilize sterile buffers with a $\text{pH}$ between 5 and 6. Aliquoting the solution is still necessary to minimize the impact of any subsequent freeze-thaw events.
• Stability: Most peptide solutions, when refrigerated at 4 degrees C (39 degrees F), remain stable for up to 30 days. Peptides with known sensitivity should be 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.