Skip to main content

Advertisement

SpringerLink
Log in

Prolactin system in the hippocampus

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

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 neuroprotective 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 synthesized 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ben-Jonathan N, Hugo E (2015) Prolactin (PRL) in adipose tissue: regulation and functions. In: Diakonova M (ed) Advances in experimental medicine and biology, vol 846. Springer International Publishing, Cham, pp 1–35

    Google Scholar 

  • Ben-Jonathan N, Mershonf JL, Allen DL, Steinmetz RW (1996) Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects. Endocr Rev 17:639–669

    CAS  PubMed  Google Scholar 

  • Brooks CL (2012) Molecular mechanisms of prolactin and its receptor. Endocr Rev 33:504–525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown RS, Wyatt AK, Herbison RE, Knowles PJ, Ladyman SR, Binart N, Banks WA, Grattan DR (2016) Prolactin transport into mouse brain is independent of prolactin receptor. FASEB J 30:1002–1010

    Article  CAS  PubMed  Google Scholar 

  • Brusco J, Wittmann R, de Azevedo M, Lcion A, Franci C, Giovenardi M, Rasia-Filho AA (2008) Plasma hormonal profiles and dendritic spines density and morphology in the hippocampal CA1 stratum radiatum, evidenced by light microscopy, of virgin and postpartum female rats. Neurosci Lett 438:346–350

    Article  CAS  PubMed  Google Scholar 

  • Cabrera V, Cantú D, Ramos E, Vanoye-Carlo A, Cerbón M, Morales T (2009) Lactation is a natural model of hippocampus neuroprotection against excitotoxicity. Neurosci Lett 461:136–139

    Article  CAS  PubMed  Google Scholar 

  • Cabrera-Reyes EA, Vergara-Castañeda E, Rivero-Segura N, Cerbón M (2015) Sex differences in prolactin and its receptor expression in pituitary, hypothalamus, ad hippocampus of the rat. Rev Mex Endocrinol Metab Nutr 2:60–67

    Google Scholar 

  • Clemens JA, Sawyer BD (1974) Identification of prolactin in cerebrospinal fluid. Exp Brain Res 21:399–402

    Article  CAS  PubMed  Google Scholar 

  • De Vito W (1988) Distribution of immunoreactive prolactin in the male and female rat brain: effects of hypophysectomy and intraventricular administration of colchicine. Neuroendocrinology 47:284–289

    Article  Google Scholar 

  • Emanuele N, Jurgens J, Halloran M, Tentler J, Lawrence A, Kelley M (1992) The rat prolactin gene is expressed in brain tissue: detection of normal and alternatively spliced prolactin messenger RNA. Mol Endocrinol 6:35–42

    CAS  PubMed  Google Scholar 

  • Ferraris J, Boutillon F, Bernadet M, Seilicovich A, Goffin V, Pisera D (2012) Prolactin receptor antagonism in mouse anterior pituitary: effects on cell turnover and prolactin receptor expression. Am J Physiol Endocrinol Metab 302:E356–E364

    Article  CAS  PubMed  Google Scholar 

  • Ferraris J, Bernichtein S, Pisera D, Goffin V (2013) Use of prolactin receptor antagonist to better understand prolactin regulation of pituitary homeostasis. Neuroendocrinology 98:171–179

    Article  CAS  PubMed  Google Scholar 

  • Fester L, Rune GM (2015) Sexual neurosteroids and synaptic plasticity in the hippocampus. Brain Res 1621:162–169

    Article  CAS  PubMed  Google Scholar 

  • Fields K, Kulig E, Lloyd R (1993) Detection of prolactin messenger RNA in mammary and other normal and neoplastic tissues by polymerase chain reaction. Lab Investig 68:354–360

    CAS  PubMed  Google Scholar 

  • Furigo IC, Ramos-Lobo AM, Frazao R, Donato J Jr (2016) Brain STAT5 signaling and behavioral control. Mol Cell Endocrinol 438:70–76

    Article  CAS  PubMed  Google Scholar 

  • Grattan DR (2015) The hypothalamo-prolactin axis. J Endocrinol 226:T101–T122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harvey S, Martínez-Moreno CG, Luna M, Arámburo C (2015) Autocrine/paracrine roles of extrapituitary growth hormone and prolactin in health and disease: an overview. Gen Comp Endocrinol 220:103–111

    Article  CAS  PubMed  Google Scholar 

  • Hirai J, Nishita M, Nakao N, Saito TR, Tanaka M (2013) Regulation of prolactin receptor gene expression in the rat choroid plexus via transcriptional activation of multiple first exons during postnatal development and lactation. Exp Anim 62:49–56

    Article  CAS  PubMed  Google Scholar 

  • Kang J-H, Hassan SA, Zhao P, Tsai-Morris CH, Dufau ML (2014) Impact of subdomain D1 of the short form S1b of the human prolactin receptor on its inhibitory action on the function of the long form of the receptor induced by prolactin. Biochim Biophys Acta 1840:2272–2280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kavarthapu R, Tsai Morris C-H, Dufau ML (2014) Prolactin induces up-regulation of its cognate receptor in breast cancer cells via transcriptional activation of its generic promoter by cross-talk between ERα and STAT5. Oncotarget 5:9079–9091

    Article  PubMed  PubMed Central  Google Scholar 

  • Kinsley CH, Trainer R, Stafisso-Sandoz G, Quadros P, Marcus LK, Hearon C, Meyer EA, Hester N, Morgan M, Kozub FJ, Lambert KG (2006) Motherhood and the hormones of pregnancy modify concentrations of hippocampal neuronal dendritic spines. Horm Behav 49:131–142

    Article  CAS  PubMed  Google Scholar 

  • Lajud N, González-Zapien R, Roque A, Tinajero E, Valdez JJ, Clapp C, Torner L (2013) Prolactin administration during early postnatal life decreases hippocampal and olfactory bulb neurogenesis and results in depressive-like behavior in adulthood. Horm Behav 64:781–789

    Article  CAS  PubMed  Google Scholar 

  • Larsen CM, Grattan DR (2012) Prolactin, neurogenesis, and maternal behaviors. Brain Behav Immun 26:201–209

    Article  CAS  PubMed  Google Scholar 

  • Lévy F, Gheusi G, Keller M (2011) Plasticity of the parental brain: a case for neurogenesis. J Neuroendocrinol 23:984–993

    Article  CAS  PubMed  Google Scholar 

  • Li J, Li W, Jiang ZG, Ghanbari HA (2013) Oxidative stress and neurodegenerative disorders. Int J Mol Sci 14:24438–24475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mariani E, Polidori MC, Cherubini A, Mecocci P (2005) Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview. J Chromatography B 827:65–75

    Article  CAS  Google Scholar 

  • Morales T, Lorenson M, Walker AM, Ramos E (2014) Both prolactin (PRL) and a molecular mimic of phosphorylated PRL, S179D-PRL, protect the hippocampus of female rats against excitotoxicity. Neuroscience 258:211–217

    Article  CAS  PubMed  Google Scholar 

  • Pardo GV, Goularte JF, Hoefel AL, de Castro AL, Kucharski LC, da Rosa AA, Lucion AB (2016) Effects of sleep restriction during pregnancy on the mother and fetuses in rats. Physiol Behav 1:66–76

    Article  CAS  Google Scholar 

  • Patil MJ, Henry MA, Akopian AN (2014) Prolactin receptor in regulation of neuronal excitability and channels. Channels (Austin) 8:193–202

    Article  Google Scholar 

  • Reyes-Mendoza J, Morales T (2016) Post-treatment with prolactin protects hippocampal CA1 neurons of the ovariectomized female rat against kainic acid-induced neurodegeneration. Neuroscience 328:58–68

    Article  CAS  PubMed  Google Scholar 

  • Rivero-Segura NA, Flores-Soto E, García de la Cadena S, Coronado-Mares I, Gómez-Verjan JC, Ferreira DG, Cabrera-Reyes EA, Lopes LV, Massieu L, Cerbón M (2017) Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca2+]i overload and NF-κB activation. PLoS One 12:e0176910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roselli CE, Bocklandt S, Stadelman HL, Wadsworth T, Vilain E, Stormshak F (2008) Prolactin expression in the sheep brain. Neuroendocrinology 87:206–215

    Article  CAS  PubMed  Google Scholar 

  • Sangeeta Devi Y, Halperin J (2014) Reproductive actions of prolactin mediated through short and long receptor isoforms. Mol Cell Endocrinol 382:400–410

    Article  CAS  PubMed  Google Scholar 

  • Swaminathan G, Varghese B, Fuchs SY (2008) Regulation of prolactin receptor levels and activity in breast cancer. J Mammary Gland Biol Neoplasia 13:81–91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tejadilla D, Cerbón M, Morales T (2010) Prolactin reduces the damaging effects of excitotoxicity in the dorsal hippocampus of the female rat independently of ovarian hormones. Neuroscience 169:1178–1185

    Article  CAS  PubMed  Google Scholar 

  • Thébault S (2017) Potential mechanisms behind the anti-oxidant actions of prolactin in the retina. Exp Eye Res 160:56–61

    Article  CAS  PubMed  Google Scholar 

  • Torner L, Karg S, Blume A, Kandasamy M, Kuhn HG, Winkler J, Aigner L, Neumann ID (2009) Prolactin prevents chronic stress-induced decrease of adult hippocampal neurogenesis and promotes neuronal fate. J Neurosci 29:1826–1833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vergara-Castañeda E, Grattan DR, Pasantes-Morales H, Pérez-Domínguez M, Cabrera-Reyes EA, Morales T, Cerbón M (2016) Prolactin mediates neuroprotection against excitotoxicity in primary cell cultures of hippocampal neurons via its receptor. Brain Res 1636:193–199

    Article  CAS  PubMed  Google Scholar 

  • Wagner K, Couillard-Despres S, Lehner B, Brockhoff G, Rivera FJ, Blume A, Neumann I, Aigner L (2009) Prolactin induces MAPK signalling in neural progenitors without alleviating glucocorticoid-induced inhibition of in vitro neurogenesis. Cell Physiol Biochem 24:397–406

    Article  CAS  PubMed  Google Scholar 

  • Walker TL, Vukovic J, Koudijs MM, Blackmore DG, Mackay EW, Sykes AM, Overall RW, Hamlin AS, Bartlett PF (2012) Prolactin stimulates precursor cells in the adult mouse hippocampus. PLoS One 7:1–11

    Google Scholar 

Download references

Author information

Author notes

  1. José Carretero and Virginia Sánchez-Robledo contributed equally to this work

Authors and Affiliations

  1. Department of Human Anatomy and Histology, Faculty of Medicine, University of Salamanca, Salamanca, Spain

    José Carretero, Marta Carretero-Hernández, Leonardo Catalano-Iniesta & Enrique J. Blanco

  2. Laboratory of Neuroendocrinology, Institute of Neurosciences of Castilla y León (INCyL), University of Salamanca, Salamanca, Spain

    José Carretero, Leonardo Catalano-Iniesta, María José García-Barrado, María Carmen Iglesias-Osma & Enrique J. Blanco

  3. Laboratory of Neuroendocrinology and Obesity, Institute for Biomedical Research of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain

    José Carretero, Virginia Sánchez-Robledo, Leonardo Catalano-Iniesta, María José García-Barrado, María Carmen Iglesias-Osma & Enrique J. Blanco

  4. Department of Physiology and Pharmacology, Faculty of Medicine, University of Salamanca, Salamanca, Spain

    Virginia Sánchez-Robledo, María José García-Barrado & María Carmen Iglesias-Osma

Authors
  1. José Carretero
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Virginia Sánchez-Robledo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marta Carretero-Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Leonardo Catalano-Iniesta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. María José García-Barrado
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. María Carmen Iglesias-Osma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Enrique J. Blanco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José Carretero.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carretero, J., Sánchez-Robledo, V., Carretero-Hernández, M. et al. Prolactin system in the hippocampus. Cell Tissue Res 375, 193–199 (2019). https://doi.org/10.1007/s00441-018-2858-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-018-2858-2

Keywords

Search

Navigation