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

IF 3.3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrinology Pub Date : 2025-06-10 DOI:10.1210/endocr/bqaf102

Mai Otsuka, Yu Takeuchi, Maho Moriyama, Sakura Egoshi, Yuki Goto, Tingting Gu, Atsushi P Kimura, Shogo Haraguchi, Taishi Yoshii, Sakae Takeuchi, Makoto Matsuyama, George E Bentley, Sayaka Aizawa

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引用次数: 0

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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神经素U缺乏扰乱大鼠每日睾酮波动并减少轮跑活动。

本研究旨在通过敲除大鼠内源性神经medin U （NMU）来阐明NMU在大鼠体内的作用。与野生型（WT）相比，雄性（而非雌性）NMU KO大鼠表现出轮跑活动的下降，尽管总体的家笼活动没有受到影响。WT大鼠血浆睾酮在一天内变化显著，在ZT1达到峰值，在ZT18达到最低点，而NMU KO大鼠血浆睾酮在一天内保持稳定。长期给予睾酮可使NMU KO大鼠的轮式跑步活动恢复到与WT大鼠相同的水平，提示NMU KO大鼠轮式跑步活动的下降是由于睾酮的昼夜变化被破坏所致。因此，NMU KO大鼠垂体前远部促黄体生成素β亚基（Lhb） mRNA的表达明显降低；免疫染色显示，在这些动物中，lh表达细胞的大小也相对较小。在雄性WT大鼠脑内，Nmu在结节部高表达，Nmu受体Nmur2在第三脑室室管膜细胞层高表达。本研究揭示了NMU的一种新功能，并表明大鼠内源性NMU通过调节睾酮来调节动机性活动。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrinology 医学-内分泌学与代谢

CiteScore

8.10

自引率

4.20%

发文量

195

审稿时长

2-3 weeks

期刊介绍： The mission of Endocrinology is to be the authoritative source of emerging hormone science and to disseminate that new knowledge to scientists, clinicians, and the public in a way that will enable "hormone science to health." Endocrinology welcomes the submission of original research investigating endocrine systems and diseases at all levels of biological organization, incorporating molecular mechanistic studies, such as hormone-receptor interactions, in all areas of endocrinology, as well as cross-disciplinary and integrative studies. The editors of Endocrinology encourage the submission of research in emerging areas not traditionally recognized as endocrinology or metabolism in addition to the following traditionally recognized fields: Adrenal; Bone Health and Osteoporosis; Cardiovascular Endocrinology; Diabetes; Endocrine-Disrupting Chemicals; Endocrine Neoplasia and Cancer; Growth; Neuroendocrinology; Nuclear Receptors and Their Ligands; Obesity; Reproductive Endocrinology; Signaling Pathways; and Thyroid.