Language

English

Publication Date

4-1-2025

Journal

Nature Metabolism

DOI

10.1038/s42255-025-01268-z

PMID

40211044

PMCID

PMC12509271

PubMedCentral® Posted Date

10-10-2025

PubMedCentral® Full Text Version

Author MSS

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 ERαvlVMH neurons in lactating mice attenuates these phenotypes. Overall, our study reveals an inhibitory effect of E2–ERαvlVMH signalling on PRL production, which is suppressed during lactation to sustain hyperprolactinemia and metabolic adaptations.

Keywords

Animals, Lactation, Female, Mice, Hyperprolactinemia, Hypothalamus, Prolactin, Estrogens, Signal Transduction, Adaptation, Physiological, Estrogen Receptor alpha, Thermogenesis, Adipose Tissue, Brown, Mice, Inbred C57BL

Published Open-Access

yes

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