The invention relates to mammal prolactin (PRL) variants having a mutation or set of mutations within the 14 N-terminal amino acids thereby preventing the formation of a disulfide bridge between Cys4 and Cys11 and, a sterically hindering mutation or set of mutations within binding site 2 of PRL. These variants are useful as antagonists of mammal prolactin receptors (PRLR), more particularly of human prolactin receptor (hPRLR).