The hypothalamic decapeptide gonadotrophin-releasing hormone (GnRH) binds to specific receptors on pituitary gonadotrophs. These receptors belong to the family of G protein-coupled receptors. Their activation leads to phosphoinositide breakdown with generation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and diacylglycerol. These second messengers initiate Ca2+ release from intracellular stores and activation of protein kinase C, both of which are important for gonadotrophin secretion and synthesis. Prolonged activation of GnRH receptors by GnRH leads to desensitization and consequently to suppressed gonadotrophin secretion. This is the primary mechanism of action of agonistic GnRH analogues. By contrast, GnRH antagonists compete with GnRH for receptors on gonadotroph cell membranes, inhibit GnRH-induced signal transduction and consequently gonadotrophin secretion. These compounds are free of agonistic actions, which might be beneficial in certain clinical applications.