Prolactin modulation of thermoregulatory circuits provides resilience to thermal challenge of pregnancy

Pregnancy represents a significant challenge to thermal homeostasis, with adaptive changes required to cope with the increased generation of metabolic heat. We have investigated the hypothesis that prolactin action in the preoptic area (POA) of the hypothalamus contributes to adaptive changes in thermoregulation during pregnancy. Prolactin receptors (Prlr) are expressed in warm-responding neurons (WRNs) in the POA, and chemogenetic activation of this subpopulation induces profound hypothermia. Adeno-associates virus (AAV)-Cre-mediated deletion of Prlr in the POA results in significant hyperthermia throughout pregnancy, suggesting that prolactin action in the POA is required for appropriate thermoregulation during pregnancy. Moreover, deletion of Prlr in glutamate neurons (including WRNs) results in markedly impaired pup survival when animals were housed at mildly elevated environmental temperatures, demonstrating that prolactin action in the POA provides resilience to thermal challenges in pregnancy. Thus, prolactin has a key role in regulating the thermoregulatory circuits, providing optimal conditions for successful pregnancy.