|dc.description.abstract||Pregnancy is associated with a significant increase in food intake. This occurs in order to supply the mother with sufficient energy to support both herself and the developing fetus throughout pregnancy and lactation when metabolic demand is high. This increase in food intake occurs despite an elevation in circulating levels of the appetite-suppressing hormone leptin. Hence, pregnancy is considered a state of leptin resistance. The hormone prolactin, the levels of which are significantly increased during pregnancy, is thought to be involved in increasing food intake during pregnancy. Exogenous administration of prolactin in rodents is associated with increased food intake and reduced response to leptin. As such, it is possible that the pregnancy-induced increases in prolactin may have the same effect. We hypothesised that prolactin acts centrally to mediate the changes in food intake that occur during pregnancy. Thus, the aim of this experiment was to measure food intake during pregnancy in mice that specifically lack prolactin receptors in the brain.
To characterise food intake in these mice, food intake and bodyweight were measured daily in non-pregnant, pregnant and lactating neuron-specific prolactin receptor knockout mice and controls. This neuron-specific prolactin receptor knockout model has lost prolactin receptors throughout the brain and thus exhibits impaired central prolactin response. Immunohistochemistry for phosphorylated signal transducer and activator of transcription 5 (pSTAT5), a marker of prolactin receptor activation, was performed in order to assess the success of the knockout animal. Finally, because there appeared to be a difference in bodyweight in the non-pregnant knockout animals, non-pregnant mice were subjected to a fast and refeed protocol and then placed on a high fat diet in order to further characterise their food intake regulatory systems.
Food intake increased significantly over pregnancy and was higher still during lactation in both animal groups. Bodyweight also increased over pregnancy, then remained stable during the lactation period. Food intake was significantly higher throughout pregnancy in the knockout animals compared with the controls. Unexpectedly, food intake and bodyweight were significantly higher in the non-pregnant knockout animals compared with the controls suggesting a basal difference in bodyweight regulation. Immunohistochemistry for pSTAT5 demonstrated significant, but not complete loss, of the prolactin receptor throughout the brain, specifically in the arcuate nucleus and medial preoptic area. There was no significant difference between the animal groups in the fast and refeed protocol. The high fat diet data demonstrated that the knockout animals on a high fat diet gained significantly more weight than the control animals on a control diet.
The results obtained did not support our hypothesis that prolactin action in the brain critically mediates changes in food intake during pregnancy. However, interpretation of these results was complicated by the non-pregnant animal results and the incomplete nature of the knockout. It remains possible the remaining prolactin-responsive neurons in the brain may mediate prolactin action to stimulate food intake. This latter interpretation is supported by the changes in bodyweight in the non-pregnant knockout animals. Despite the failure to support or disprove our hypothesis, a significant step towards characterisation of this knockout model was made.||