Tesamorelin

Tesamorelin is a synthetic analogue of growth hormone releasing hormone (GHRH) with a modified N-terminal sequence — a trans-3-hexenoyl moiety is added to the N-terminal tyrosine, conferring increased resistance to DPP-4 degradation and enhanced stability compared to native GHRH or sermorelin. Upon binding the GHRH receptor (GHRHR) on pituitary somatotropes, tesamorelin activates Galphas/cAMP/PKA signalling, stimulating growth hormone synthesis and release. The N-terminal modification extends tesamorelin's half-life relative to sermorelin while retaining GHRH receptor agonist activity, producing a pharmacokinetic profile intermediate between the short-acting sermorelin (~10 minutes) and the very long-acting CJC-1295 with DAC (~8 days). Tesamorelin is specifically studied for its effects on visceral adipose tissue (VAT) lipolysis: GH release stimulated by tesamorelin activates GH receptor signalling in visceral adipocytes, promoting hormone-sensitive lipase activation and lipolysis specifically in the visceral fat depot. This VAT-selective lipolytic effect distinguishes tesamorelin's research profile — the compound is studied both as a GHRH analogue for GH release research and as a tool for investigating GH-mediated visceral adipose tissue metabolism, the fat depot most strongly associated with metabolic health risk.