Prolactin and the prolactin receptor: new targets of an old hormone

Prolactin (PRL) is one of a family of related hormones including growth hormone (GH) and placental lactogen (PL) that are hypothesized to have arisen from a common ancestral gene about 500 million years ago. Over 300 different functions of PRL have been reported, highlighting the importance of this pituitary hormone. PRL is also synthesized by a number of extra-pituitary tissues including the mammary gland and the uterus. Most of PRL's actions are mediated by the unmodified 23 kDa peptide, however, PRL may be modified post-translation, thereby altering its biological effects. PRL exerts these effects by binding to its receptor, a member of the class I cytokine receptor superfamily. This activates a number of signaling pathways resulting in the transcription of genes necessary for the tissue specific changes induced by PRL. Mouse knockout models of the major forms of the PRL receptor have confirmed the importance of PRL's role in reproduction. Further knockout models have provided insight into the importance of PRL signaling intermediates and the advent of transcript profiling has allowed the elucidation of a number of PRL target genes.