Tesamorelin

Tesamorelin Overview

Tesamorelin is a synthetic analog of growth hormone-releasing hormone (GHRH) comprised of the 44 amino acids of human GHRH with a hexenoyl modification at the N-terminus. Clinical research has demonstrated that Tesamorelin effectively elevates IGF-1 levels in subjects by an average of 181 micrograms per liter. It functions by binding to and activating human GHRH receptors with a potency and selectivity comparable to endogenous GHRH produced by the hypothalamus.

Beyond its primary role in stimulating the pulsatile release of growth hormone from the pituitary gland, Tesamorelin is a subject of intense study for its diverse metabolic and physiological effects. Research indicates it may offer neuroprotective benefits, potentially enhancing cognitive functions (nootropic effects) and improving lipid profiles by lowering triglyceride levels. Further clinical investigations have highlighted its ability to reduce carotid intima-media thickness (cIMT), visceral adipose tissue (VAT), and C-reactive protein (CRP) levels, which are key markers of cardiovascular and metabolic health. Significantly, Tesamorelin does not appear to disrupt the regulatory mechanisms of other pituitary hormones, making it a highly targeted tool in endocrine research.

Tesamorelin Peptide Structure

The stability and biological activity of Tesamorelin are attributed to specific chemical modifications at both ends of the peptide chain. These modifications protect the molecule from rapid enzymatic degradation by dipeptidyl peptidase-4 (DPP-4), extending its half-life compared to natural GHRH.

Chemical Identification: N-(trans-3-hexenoyl)-[Tyr1]hGHRF(1-44)NH2 acetate

Structure Solution Formula: C221H366N72O67S

Molecular Component Breakdown:

• N-Terminus: Modified with a trans-3-hexenoyl group to provide resistance against aminopeptidases.
• C-Terminus: Modified with an acetyl group to enhance overall structural stability.
• Amino Acid Chain: A 44-amino acid sequence that mirrors the bioactivity of natural human GHRH.

Tesamorelin Research

Tesamorelin Peptide and Lipodystrophy

Lipodystrophy involves a pathological redistribution of body fat, often manifesting as localized fat loss alongside excessive accumulation in the abdominal region. This condition is frequently comorbid with insulin resistance and dyslipidemia. In Phase III clinical trials involving 806 participants over 52 weeks (including a 26-week extension), Tesamorelin treatment resulted in a 15.4% reduction in visceral adipose tissue (VAT). Additionally, researchers noted significant improvements in cholesterol and triglyceride profiles compared to the placebo control groups.

Immunodeficient Fat Fractions and Hepatic Health

Severe immunodeficiencies are often linked to the development of non-alcoholic fatty liver disease (NAFLD). A 12-month clinical trial focused on HIV-positive participants with elevated hepatic fat fraction (HFF). Results showed that 35% of those treated with Tesamorelin achieved a reduction in liver fat of at least 5%, whereas only 4% of the placebo group reached the same threshold. Notably, these metabolic improvements occurred without adversely affecting glucose homeostasis.

Impact on Muscle Tissue Composition

Researchers utilized computed tomography (CT) imaging to assess how Tesamorelin influences body composition beyond fat loss. The data revealed significant increases in muscle density and cross-sectional area in the rectus abdominis, psoas major, and paraspinal muscles. Furthermore, Tesamorelin was associated with a decrease in intramuscular fat, suggesting an improvement in overall muscle quality and structural integrity.

Cognitive Health and Neuroprotection

Investigations into the nootropic potential of Tesamorelin suggest it may support cognitive health in older adults and those with mild cognitive impairment. By modulating the GHRH-GH-IGF-1 axis, Tesamorelin may influence brain health and executive function. Ongoing trials are specifically looking at the Global Deficit Score in populations at high risk for neurodegenerative conditions like Alzheimer’s disease.

Summary of Research Findings

Research Focus

Primary Outcome Observed

Impact Level

Visceral Adipose Tissue

Average reduction of 15% to 25%

Significant

IGF-1 Levels

Mean increase of 122% to 181 mcg/L

High

Hepatic Fat (HFF)

35% of subjects saw >5% reduction

Moderate

Triglycerides

Notable decrease in circulating lipids

Significant

Muscle Integrity

Increased density; decreased fat infiltration

Notable

Glucose Metabolism

Minimal to no change in insulin sensitivity

Neutral

Article Author

Scientific Journal Author

Reference Citations

1. 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/
2. Spooner, L. M., and 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.106291
3. Stanley TL, Chen CY, Branch KL, Makimura H, Grinspoon SK. Effects of a growth hormone-releasing hormone analog on endogenous GH 2pulsatility 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.
4. Ferdinandi ES, Brazeau P, High K, Procter B, Fennell S, Dubreuil P. Non-clinical pharmacology and safety evaluation of TH9507, a human 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: 17214611.34
5. Stanley, T. L., Fourman, L. T., Feldpau5sch, M. N., Purdy, J., Zheng, I., Pa6n, 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., and 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-e830.78
6. Falutz J, Mamputu JC, Potvin D, Moyle G, Soulban9 G, Loughrey H, Marsolais C, Turner R, Grinspoon S. Effects of tesamorelin (TH9507), a growth 10hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two mu11lticenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010 Sep;95(9):4291-304.
7. Tesamorelin Effects on Liver Fat and Histology in HIV. https://clinicaltrials.gov/ct2/show/NCT02196831
8. Phase II Trial of Tesamorelin for Cognition in Aging HIV-Infected Persons. https://clinicaltrials.gov/ct2/show/record/NCT02572323
9. Clemmons, D. R., Miller, S., and 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), e0179538.1213
10. Adrian S, Scherzinger A, Sanyal A, Lake JE, Falutz J, Dube MP, Stanley T, Grinspoon S, Ma14mputu JC, Marsolais C15, 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.
11. 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.

Storage

Storage Instructions

All products undergo a rigorous lyophilization (freeze-drying) process. This state ensures molecular stability during transit for approximately 3 to 4 months. Once the peptide is reconstituted with bacteriostatic water, it must be stored in a refrigerated environment between 2 and 8 degrees Celsius (36 to 46 degrees Fahrenheit). Reconstituted solutions remain stable for a maximum of 30 days.

Lyophilization, or cryodesiccation, involves freezing the peptide and reducing the surrounding pressure to allow the frozen water to sublimate directly from the solid phase to the gas phase. This leaves a "cake" or crystalline powder that is highly stable at room temperature for short durations. For long-term preservation exceeding several months, the lyophilized powder should be stored in a freezer at -80 degrees Celsius (-112 degrees Fahrenheit) to prevent structural degradation.

Preventing Oxidation and Moisture Contamination

Exposure to atmospheric oxygen and moisture is the primary cause of peptide degradation. To prevent condensation, always allow the vial to reach room temperature before opening the seal. Minimize the time the container remains open and consider backfilling the vial with an inert gas like nitrogen if available in a laboratory setting. Peptides containing sensitive residues such as methionine or tryptophan require strict adherence to these protocols to avoid oxidation.

Storing Peptides in Solution

Peptides in a liquid state are significantly more fragile and susceptible to bacterial growth. If a solution must be stored, use a sterile buffer with a pH of 5 to 6. It is recommended to divide the solution into single-use aliquots to avoid repeated freeze-thaw cycles, which can shear the peptide bonds and render the product ineffective.

Peptide Storage Containers

Storage vessels should be chemically inert and durable. High-quality borosilicate glass vials are preferred for their stability and clarity. If using plastic, polypropylene is recommended over polystyrene due to superior chemical resistance. Vials should be sized appropriately to minimize the "headspace" of air inside the container.

Peptide Storage Guidelines: General Tips

• Store in a cool, dry, and dark environment at all times.
• Strictly avoid repeated freeze-thaw cycles to maintain molecular integrity.
• Keep exposure to ambient air to an absolute minimum.
• Protect the product from direct light exposure to prevent photo-degradation.
• Prioritize keeping the peptide in its lyophilized state for as long as possible.
• Utilize aliquoting techniques to ensure only the necessary amount is handled at one time.