Lonapegsomatropin

Lonapegsomatropin-tcgd undergoes autocleavage to release active somatropin from the methoxypolyethylene glycol carrier. Somatropin binds to the growth hormone receptor leading to direct effects and insulin-like growth factor-1 mediated indirect effects. Somatropin has effects on the epiphyses of long bones, leading to growth in pediatric patients. Somatropin also stimulates chondrocyte differentiation and proliferation, release of glucose from the liver, protein synthesis, and lipolysis.

Somatotropin mediates its effects both directly by somatotropin and indirectly by insulin-like growth factor-1 (IGF-1), which is upregulated by growth hormone. It binds to the human growth hormone receptor (GHR), which is a dimeric receptor expressed in target cells in the liver and cartilage. Upon binding of growth hormone, GHR dimerizes and interacts with Janus kinase 2 (JAK2), subsequently leading to tyrosine phosphorylation of JAK2 and the GH receptor. The signal transducer activator of transcription (STAT) pathway is initiated, where transcription factors such as STAT1, STAT3, and STAT5 are translocated into the nucleus to stimulate target gene transcription.

At the epiphysis or growth plate, growth hormone increases linear growth by promoting differentiation of prechondrocytes and expansion of osteoblasts. Growth hormone binding to its receptor in the liver and cartilage promotes the production of IGF-1, which acts on type 1 IGF receptors to also stimulate linear growth. In the liver, activated growth hormone receptor signalling leads to increased production of IGF binding protein-3 (IGFBP-3) and acid-labile subunit (ALS), which are proteins that bind to IGF-1 in a ternary complex to increase its half-life.