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Key Points The major 23 kDa prolactin isoform exerts its action via a transmembrane receptor, prolactin receptor (PRL-R), which belongs to the class of haematopoietic cytokine receptors Binding of prolactin to its predimerized receptor induces a conformational change in the receptor, which enables signal transduction Hyperprolactinaemia causes hypogonadotropic hypogonadism by inhibiting kisspeptin-1 secretion, which in turn disrupts hypothalamic gonadotropin-releasing hormone I secretion The first germline loss-of-function mutation in the gene that encodes PRL-R was reported in three sisters with familial idiopathic hyperprolactinaemia The 16 kDa isoform of prolactin has antitumoral and antiangiogenic actions and is involved in peripartum cardiomyopathy Abstract Prolactin is a hormone that is mainly secreted by lactotroph cells of the anterior pituitary gland, and is involved in many biological processes including lactation and reproduction

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Peer review Peer review information Nature Chemical Biology thanks Rudi Fasan and the other, anonymous reviewer(s) for their contribution to the peer review of this work