REVIEW Prolactin system in the hippocampus José Carretero 1,2,3 & Virginia Sánchez-Robledo 3,4 & Marta Carretero-Hernández 1 & Leonardo Catalano-Iniesta 1,2,3 & María José García-Barrado 2,3,4 & María Carmen Iglesias-Osma 2,3,4 & Enrique J. Blanco 1,2,3 Received: 25 January 2018 /Accepted: 11 May 2018 /Published online: 28 May 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Among the more than 300 biological actions described for prolactin, its role in the neurogenic capacity of the hippocampus, which increases synaptogenesis and neuronal plasticity, consolidates memory and acts as a neuronal protector against excitotoxicity—effects mediated through its receptors are more recently known. The detection of prolactin in the hippocampus and its receptors, specifically in the Ammon’ s horn and dentate gyrus, opened up a new field of study on the possible neuro- protective effect of hormones in a structure involved in learning and memory, as well as in emotional and behavioral processes. It is currently known, although controversial, that prolactin may be related to sex and age and that the hormone could be synthe- sized in the hippocampus itself. However, the regulatory mechanisms of changes in prolactin or in its hippocampal receptors still remain unknown. This review introduces the reader to general aspects concerning prolactin and its receptors and to what is currently known about the role prolactin plays in the brain and, in particular, in the hippocampus. Keywords Prolactin . Hippocampus . Prolactin receptor . Neuroprotection . Learning and memory Prolactin and its receptor Prolactin (PRL) is a peptide hormone present in all vertebrates. It is phylogenetically well-conserved (Brooks 2012) and is known to have more than 300 different biological functions, including the stimulation of neurogenesis, modulation of stress responses, calcium transport, immune system regulation and reduction of anxiety, among others (Larsen and Grattan 2012; Ferraris et al. 2013; Patil et al. 2014). The synthesis of prolactin occurs mainly in the anterior pituitary and it is released into the peripheral blood in a pul- satile manner. Prolactin acts on its specific receptor, PRLR, which be- longs to the transmembrane type I cytokine receptor super- family. PRLR is encoded by a single gene located on chromo- somes 5, 15 and 2 in humans, mice and rats, respectively, with multiple specific variants in numerous tissues and cell types (Patil et al. 2014; Sangeeta Devi and Halperin 2014). This gene has a complex genomic structure, which includes the presence of a promoter region and multiple first exons whose alternative activation regulates the transcription of the gene (Swaminathan et al. 2008). Up to five first exons have been described in rat, designated E11, E12, E13, E14 and E15, where exon E14 seems to be responsible for the expression of the PRLR gene throughout development and especially in the choroidal plexuses during postnatal development and lacta- tion (Tejadilla et al. 2010; Hirai et al. 2013). Variants of the receptor can be generated by alternative splicing of the first transcript or by post-transcriptional divi- sion, obtaining different isoforms that share a large part of the structure and that constitute the two halves of the complete José Carretero and Virginia Sánchez-Robledo contributed equally to this work * José Carretero jcar@usal.es 1 Department of Human Anatomy and Histology, Faculty of Medicine, University of Salamanca, Salamanca, Spain 2 Laboratory of Neuroendocrinology, Institute of Neurosciences of Castilla y León (INCyL), University of Salamanca, Salamanca, Spain 3 Laboratory of Neuroendocrinology and Obesity, Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain 4 Department of Physiology and Pharmacology, Faculty of Medicine, University of Salamanca, Salamanca, Spain Cell and Tissue Research (2019) 375:193–199 https://doi.org/10.1007/s00441-018-2858-2