From the molecular biology of prolactin and its receptor to the lessons learned from knockout mice models

Prolactin (PRL). a polypeptide hormone secreted mainly by the pituitary and , to a lesser extent, by peripheral tissues, affects more physiological pro cesses than all other pituitary hormones combined since it is involved in > 300 separate functions in vertebrates. Its main actions are related to lac tation and reproduction. The initial step of PRL action is the binding to a specific membrane receptor, the PRLR, which belongs to the class 1 cytokin e receptor superfamily. PRL-binding sites have been identified in a number of tissues and cell types in adult animals. Signal transduction by this rec eptor is mediated, at least in part, by two families of signaling molecules : Janus tyrosine kinases and signal transducers and activators of transcrip tion (STATs). Disruption of the PRLR gene has provided a new mouse model wi th which to identify actions directly associated with PRL or any other PRLR ligands, such as placental lactogens. To date, several different phenotype s have been analyzed and are briefly described in this review. Coupled with the SAGE technique, this PRLR knockout model is being used to qualitativel y and quantitatively evaluate the expression pattern of hepatic genes in tw o physiological situations: transcriptomes corresponding to livers from bot h wild type and PRLR KO mice are being compared, and following statistical analyses, candidate genes presenting a differential profile will be further characterized. Such a new approach will undoubtedly open future avenues of research for PRL targets. To date, no pathology linked to any mutation in the genes encoding PRL or its receptor have been identified. The developmen t of genetic models provides new opportunities to understand how PRL can pa rticipate to the development of pathologies throughout life, as for example the initiation and progression of breast cancer, (C) 1999 Elsevier Science B.V. All rights reserved.