Suppression of hypothalamic oestrogenic signal sustains hyperprolactinemia and metabolic adaptation in lactating mice

IF 18.9 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Nature metabolism Pub Date : 2025-04-10 DOI:10.1038/s42255-025-01268-z

Meng Yu, Bing Feng, Jonathan C. Bean, Qianru Zhao, Yongjie Yang, Hailan Liu, Yongxiang Li, Benjamin P. Eappen, Hesong Liu, Longlong Tu, Kristine M. Conde, Mengjie Wang, Xi Chen, Na Yin, Darah Ave Threat, Nathan Xu, Junying Han, Peiyu Gao, Yi Zhu, Darryl L. Hadsell, Yang He, Pingwen Xu, Yanlin He, Chunmei Wang

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Abstract

17β-oestradiol (E2) inhibits overeating and promotes brown adipose tissue (BAT) thermogenesis, whereas prolactin (PRL) does the opposite. During lactation, the simultaneous decline in E2 and surge in PRL contribute to maternal metabolic adaptations, including hyperphagia and suppressed BAT thermogenesis. However, the underlying neuroendocrine mechanisms remain unclear. Here, we find that oestrogen receptor alpha (ERα)-expressing neurons in the medial basal hypothalamus (MBH), specifically the arcuate nucleus of the hypothalamus and the ventrolateral subdivision of the ventromedial hypothalamus (vlVMH), are suppressed during lactation. Deletion of ERα from MBH neurons in virgin female mice induces metabolic phenotypes characteristic of lactation, including hyperprolactinemia, hyperphagia and suppressed BAT thermogenesis. By contrast, activation of ERα^vlVMH neurons in lactating mice attenuates these phenotypes. Overall, our study reveals an inhibitory effect of E2–ERα^vlVMH signalling on PRL production, which is suppressed during lactation to sustain hyperprolactinemia and metabolic adaptations.

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来源期刊

Nature metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

27.50

自引率

2.40%

发文量

170

期刊介绍： Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.