Elevated Prolactin during Pregnancy Drives a Phenotypic Switch in Mouse Hypothalamic Dopaminergic Neurons

Siew Yip (1) , Nicola Romanò (2) , Papillon Gustafson (1) , David Hodson (3) , Eloise Williams (1) , Ilona Kokay (1) , Agnès O Martin (2) , Patrice Mollard (2) , David Grattan (1) , Stephen Bunn (1)

1 University of Otago [Dunedin, Nouvelle-Zélande]
2 IGF - Institut de Génomique Fonctionnelle
3 University of Birmingham [Birmingham]

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.

Domaines: Neurobiologie; Endocrinologie et métabolisme; Gynécologie et obstétrique

Siew Yip, Nicola Romanò, Papillon Gustafson, David Hodson, Eloise Williams, et al.. Elevated Prolactin during Pregnancy Drives a Phenotypic Switch in Mouse Hypothalamic Dopaminergic Neurons. Cell Reports, 2019, 26 (7), pp.1787-1799.e5. ⟨10.1016/j.celrep.2019.01.067⟩. ⟨hal-02370606⟩