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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

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Materials and methods A

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

Enhanced fat oxidation and improved energy availability