Neuromedin U partly mimics thyroid stimulating hormone and triggers Wnt/β-Catenin signalling in the photoperiodic response of F344 rats

In seasonal animals, photoperiod exerts profound effects on physiology, such as growth, energy balance and reproduction, through changes in the neuroendocrine axes. A key element of the photoperiodic response is the thyroid hormone level in the hypothalamus which is controlled via retrograde transport of thyroid-stimulating hormone (TSH) from the pars tuberalis of the pituitary. TSH regulates type II deiodinase (Dio2) expression, which transforms inactive thyroid hormone to its active form, through TSH receptors expressed in the ependymal cells of the hypothalamus. In this study we hypothesised that a second peptide hormone Neuromedin U (NMU) may play a role in the photoperiodic response alongside TSH, since the NMU gene is also expressed in a strongly photoperiod-dependent manner in the pars tuberalis and its receptor NMU2 is expressed in the ependymal layer of the third ventricle in photoperiod-sensitive F344 rats. Consistent with other studies in non-seasonal mammals, we found that acute intracerebroventricular injections of NMU into the hypothalamus negatively regulated food intake and body weight and increased core body temperature in F344 rats. At the same time NMU increased Dio2 mRNA expression in the ependymal region of the hypothalamus similar to the effects of TSH. These data suggest that NMU may affect acute and photoperiodically controlled energy balance through distinct pathways. We also showed that TSH inhibits expression of type III deiodinase (Dio3) in F344 rats, a response not mimicked by NMU. Furthermore, NMU also increased expression of genes from the Wnt/β-Catenin pathway within the ependymal layer of the third ventricle. This effect was not influenced by TSH. These data indicate that while NMU acts with some similarities to TSH, it also has completely distinct signalling functions that do not overlap. In summary, this work on NMU signalling reveals the potential for a new player in the control of seasonal biology. This article is protected by copyright. All rights reserved.