Protein and peptide hormone action

Protein and peptide hormones cannot pass through the cell membrane. Therefore, in order to be able to affect cellular processes, there should be a way to transfer their message through the cell membrane. This is generally performed by transmembrane receptors, which have an extracellular part able to recognize the hormone, and an intracellular part which transfers the activity to intracellular signal transduction pathways. Binding of the hormone to members of the G-protein coupled receptor (GPCR) family leads to dissociation of GDP from G-proteins, enabling association of GTP with a G-protein a-subunit leading to the production of second messengers. GPCRs are involved in signal transduction of a large number of hormones, such as biogenic amines, and peptide and protein hormones. Ligand binding to kinase-linked receptors usually leads to multimerization of receptors, followed by activation of the receptors by mutual phosphorylation at serine/threonine or tyrosine residues and subsequent phosphorylation of intracellular proteins which can transfer the hormonal message to the nucleus or other intracellular targets. Examples of this group are receptors for insulin, growth hormone (GH) and members of the TGFΒ-family of growth factors. After activation of the receptor at the cell membrane, subsequent receptor internalization can enhance the action of the hormone by continuation of receptor action after incorporation in endosomes, or alternatively terminate signaling by lysosomal degradation of the hormone-receptor complex. Finally, activity of the receptors can be affected by the action of synthetic or endogenous agonists and antagonists.