Possible crosstalk between leptin and prolactin during pregnancy

Rodents exhibit leptin resistance and high levels of prolactin/placental lactogens during pregnancy. A crosstalk between prolactin and leptin signaling has been proposed as a possible mechanism to explain the changes in energy balance during gestation. However, it remains unclear if specific neuronal populations co-express leptin and prolactin receptors. Therefore, our present study was undertaken to identify in the mouse brain prolactin-responsive cells that possibly express the leptin receptor (LepR). In addition, we assessed the leptin response in different brain nuclei of pregnant and nulliparous mice. We used a LepR-reporter mouse to visualize LepR-expressing cells with the tdTomato fluorescent protein. Prolactin-responsive cells were visualized with the immunohistochemical detection of the phosphorylated form of the signal transducer and activator of transcription-5 (pSTAT5-ir). Notably, many neurons that co-expressed tdTomato and pSTAT5-ir were observed in the medial preoptic area (MPA, 27-48% of tdTomato cells), the retrochiasmatic area (34-51%) and the nucleus of the solitary tract (NTS, 16-24%) of prolactin-treated nulliparous mice, pregnant mice and prolactin-treated leptin-deficient (ob/ob) mice. The arcuate nucleus of the hypothalamus (8-22%), the medial tuberal nucleus (11-15%) and the ventral premammillary nucleus (4-10%) showed smaller percentages of double-labeled cells among the groups. Other brain nuclei did not show significant percentages of neurons that co-expressed tdTomato and pSTAT5-ir. Late pregnant mice exhibited a reduced leptin response in the MPA and NTS when compared with nulliparous mice; however, a normal leptin response was observed in other brain nuclei. In conclusion, our findings shed light on how the brain integrates the information conveyed by leptin and prolactin. Our results corroborate the hypothesis that high levels of prolactin or placental lactogens during pregnancy may directly interfere with LepR signaling, possibly predisposing to leptin resistance.