Human PRLR binds at least 3 related peptide ligands namely prolactin, placental lactogen (PL) and growth hormone (GH). In non primates, GH is not able to bind the PRLR. Human GH binding to the PRLR is zinc-dependent (Cunningham et al. 1990). All three ligands bind the extracellular domain and have apparently identical actions. Two disulfide-linked cysteines in the D1 subdomain are involved in ligand binding while the WSXWS motif in the D2 subdomain is probably required for folding and cellular trafficking.