Differential regulation of leptin receptor but not orexin in the hypothalamus of the lactating rat

During lactation, hypothalamic levels of neuropeptide Y (NPY) and agouti re lated protein (AGRP) mRNA are increased, while pro-opiomelanocortin (POMC) mRNA is decreased. Serum leptin levels are also decreased during lactation. These changes may underlie the large increases of both food and water inta ke that occur in concert with milk production. However, additional hypothal amic substances, such as the novel peptide, orexin, may be involved. In add ition, in the presence of chronically suppressed levels of serum leptin, th ere may be a change in leptin receptor expression in the hypothalamus. The objectives of the present study were to determine if orexin and leptin rece ptor mRNA levels were changed during lactation. Rats were studied on dioest rus of the oestrous cycle or on day 10 postpartum (the lactating animals we re suckling eight pups). Orexin mRNA levels in the lateral hypothalamus did not differ between dioestrus and lactation. There was a significant increa se in leptin receptor mRNA levels in the supraoptic nucleus during lactatio n compared to dioestrus. Furthermore, leptin receptor protein, as determine d by immunocytochemistry, was colocalized in virtually all vasopressin and oxytocin cells in the supraoptic nucleus. Lactating animals exhibited a dec rease in leptin receptor mRNA in the ventromedial hypothalamic nucleus wher eas no change was apparent in other hypothalamic areas compared to the dioe strus animals. These results demonstrate that changes in orexin do not appe ar to contribute to the increase in food intake during lactation. It is lik ely that the increases in NPY and ARGP, coupled with the decrease in POMC, are primarily responsible for sustaining the chronic hyperphagia of lactati on. The changes observed in leptin receptor expression in the hypothalamus, along with the suppression of serum leptin levels, also suggest that the l eptin signalling system may play a significant role in the regulation of fo od and water intake during lactation.