Neuromedin U Deficiency Disrupts Daily Testosterone Fluctuation and Reduces Wheel-Running Activity in Rats

TL;DR

This study shows that Neuromedin U in rats helps regulate daily testosterone changes and wheel-running activity.

Contribution

The study reveals a novel role of Neuromedin U in regulating testosterone and motivated behavior in male rats.

Findings

NMU knockout male rats showed reduced wheel-running activity compared to wildtype rats.

NMU deficiency disrupts daily testosterone fluctuations in male rats.

Testosterone administration restored wheel-running activity in NMU knockout rats.

Abstract

The objective of this study was to elucidate the role of endogenous Neuromedin U (NMU) in rats by performing NMU knockout (KO). Male, but not female NMU KO rats exhibited decreased wheel-running activity vs wildtype (WT), although overall home cage activity was not affected. Plasma testosterone in WT rats varied significantly over the course of a day, with a peak at ZT1 and a nadir at ZT18, whereas in NMU KO rats testosterone remained stable throughout the day. Chronic administration of testosterone restored wheel-running activity in NMU KO rats to the same level as in WT rats, suggesting that the decrease in wheel-running activity in NMU KO rats is due to the disruption of the diurnal change of testosterone. Accordingly, expression of the luteinizing hormone beta subunit (Lhb) mRNA in the pars distalis of anterior pituitary was significantly lower in NMU KO rats; immunostaining revealed that the size of luteinizing hormone (LH)–expressing cells was also relatively small in those animals. In the brain of male WT rats, Nmu was highly expressed in the pars tuberalis, and the NMU receptor Nmur2 was highly expressed in the ependymal cell layer of the third ventricle. This study reveals a novel function of NMU and indicates that endogenous NMU in rats plays a role in the regulation of motivated activity via regulation of testosterone.

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