Elevated Prolactin during Pregnancy Drives a Phenotypic Switch in Mouse Hypothalamic Dopaminergic Neurons
Siew H. Yip,
Nicola Romanò,
Papillon Gustafson,
David J. Hodson,
Eloise J. Williams,
Ilona C. Kokay,
Agnes O. Martin,
Patrice Mollard,
David R. Grattan,
Stephen J. Bunn
Affiliations
Siew H. Yip
Department of Anatomy, University of Otago, Dunedin 9054, New Zealand; Centre for Neuroendocrinology, University of Otago, Dunedin 9054, New Zealand
Nicola Romanò
Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh EH8 9XD, Scotland
Papillon Gustafson
Department of Anatomy, University of Otago, Dunedin 9054, New Zealand; Centre for Neuroendocrinology, University of Otago, Dunedin 9054, New Zealand
David J. Hodson
Institute of Metabolism and Systems Research (IMSR) and Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Edgbaston B15 2TT, UK; Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham Health Partners, Birmingham B15 2TH, UK
Eloise J. Williams
Department of Anatomy, University of Otago, Dunedin 9054, New Zealand; Centre for Neuroendocrinology, University of Otago, Dunedin 9054, New Zealand
Ilona C. Kokay
Department of Anatomy, University of Otago, Dunedin 9054, New Zealand; Centre for Neuroendocrinology, University of Otago, Dunedin 9054, New Zealand
Agnes O. Martin
IGF, CNRS, INSERM, Université de Montpellier, Montpellier, France
Patrice Mollard
IGF, CNRS, INSERM, Université de Montpellier, Montpellier, France
David R. Grattan
Department of Anatomy, University of Otago, Dunedin 9054, New Zealand; Centre for Neuroendocrinology, University of Otago, Dunedin 9054, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland 1010, New Zealand
Stephen J. Bunn
Department of Anatomy, University of Otago, Dunedin 9054, New Zealand; Centre for Neuroendocrinology, University of Otago, Dunedin 9054, New Zealand; Corresponding author
Summary: Altered physiological states require neuronal adaptation. In late pregnancy and lactation, a sub-population of the mouse hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons alters their behavior to synthesize and release met-enkephalin rather than dopamine. These neurons normally release dopamine to inhibit prolactin secretion and are activated by prolactin in a short-loop feedback manner. In lactation, dopamine synthesis is suppressed in an opioid-dependent (naloxone-reversible) manner, meaning that prolactin secretion is disinhibited. Conditional deletion of the prolactin receptor in neurons reveals that this change in phenotype appears to be driven by prolactin itself, apparently through an alteration in intracellular signaling downstream of the prolactin receptor that favors enkephalin production instead of dopamine. Thus, prolactin effectively facilitates its own secretion, which is essential for lactation and maternal behavior. These studies provide evidence of a physiologically important, reversible alteration in the behavior of a specific population of hypothalamic neurons in the adult brain. : Pituitary prolactin secretion is inhibited by dopamine released by hypothalamic neurons. Yip et al. show that, during lactation, these TIDA neurons alter their response to prolactin and release enkephalin in place of dopamine. This mechanism promotes rather than inhibits prolactin secretion, supporting its elevation during lactation. Keywords: prolactin, prolactin receptor, dopamine, encephalin, hypothalamus, tuberoinfundibular dopaminergic neurons, neuronal plasticity, lactation, lactotrophs
