Negative energy balance and leptin regulate neuromedin-U expression in the rat pars tuberalis

Abstract

Central neuromedin U (NMU) functions in energy balance, the hypothalamic-pituitary-adrenal axis, LH release and circadian rhythmicity. In rats, high levels of NMU occur in the hypothalamic suprachiasmatic nuclei and the pars tuberalis of the pituitary. NMU expression in the pars tuberalis appears to be downregulated in the Zucker fatty (fa/fa) rat, lacking functional leptin receptors. In contrast, in the dorsomedial (DMH) nuclei of the mouse, NMU expression is higher in the ob/ob mouse, lacking leptin, and is upregulated by fasting. However, leptin appears not to change NMU gene expression in either the mouse DMH or the rat pars tuberalis. Thus, the present study aims to better identify factors influencing central NMU expression in the rat pars tuberalis. Sprague-Dawley rats were fasted and/or challenged with intracerebroventricular leptin or ghrelin and gene expression was measured using real-time reverse transcriptase-PCR and quantitative in situ hybridisation with riboprobes specific for NMU and NMU receptor (NMU-R2). NMU expression in the rat pars tuberalis was elevated by fasting. Ghrelin administration had no effect on the level of NMU expression, but leptin was found to diminish the expression in a concentration- and time-dependent manner. NMU-R2 expression was unchanged in any of the groups measured. These results suggest that NMU expression in rat pars tuberalis is upregulated in states of negative energy balance, and this may be mediated indirectly by changes in leptin levels. These results demonstrate a link between energy balance and NMU expression in the pars tuberalis of the pituitary.