Evidence mapPaperPMID 40920933Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Muricholic acid mediates puberty initiation via the hypothalamic TGR5 signaling pathway.

Shan Wang, Ke Huang, Ana Liu, Senjie Wang, Runqiu Jiang, Wenlian Chen, Huiying Wang, Rahim Ullah, Chuqing Xue, Wei Wu and 4 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Shan WangDepartment of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Ke HuangDepartment of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Ana LiuDepartment of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Senjie WangDepartment of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Runqiu JiangDepartment of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210093, China.
Wenlian ChenCancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.ORCID 0000-0002-1359-2549
Huiying WangDepartment of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Rahim UllahDepartment of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Chuqing XueDepartment of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Wei WuDepartment of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Guanping DongDepartment of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Peifang JiangDepartment of Neurology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Junfen FuDepartment of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.ORCID 0000-0001-6405-1251
Yan NiDepartment of Endocrinology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.ORCID 0000-0003-1779-7266

Funding

Key Research and Development Program of Zhejiang Province (Key R&D plan of Zhejiang Province) 2023C03047MOST | National Key Research and Development Program of China (NKPs) 2021YFC2701901MOST | National Natural Science Foundation of China (NSFC) 82170583MOST | National Natural Science Foundation of China (NSFC) 82370863
6 · The paper itself

Abstract

The onset of puberty is increasingly observed at earlier ages in children, especially in girls with obesity, a trend that predisposes them to long-term metabolic and reproductive disorders in adulthood. Bile acids have emerged as pivotal signaling molecules in both metabolic and reproductive disorders, but remain unexplored in the early onset of puberty in children. Herein, we find elevated levels of muricholic acid (MCA) species in the serum of girls with central precocious puberty, which strongly correlate with indices of hypothalamic-pituitary-gonadal axis activation and can reach peak levels during puberty among healthy children. Intriguingly, reduction of MCA species can lead to decreased expression of gonadotropin-releasing hormone (GnRH) and delay the early onset of puberty, while elevated MCA levels induced premature sexual development in female mice. Mechanistically, we demonstrated that MCA had strong activation effects on Takeda G-protein-coupled receptor 5 (TGR5), and MCA enhanced GnRH expression in GnRH neurons through activation of the TGR5-PI3K/Akt-mTOR signaling pathway. Our findings reveal a link between metabolic status and reproductive maturation, highlighting MCA as a potential therapeutic target for managing early puberty initiation.

Indexed as

HypothalamusPubertyPuberty, PrecociousReceptors, G-Protein-CoupledSignal TransductionAnimalsChildFemaleGonadotropin-Releasing HormoneHumansMiceNeuronsPhosphatidylinositol 3-KinasesSexual MaturationTOR Serine-Threonine KinasesGonadotropin-Releasing HormoneGPBAR1 protein, humanGpbar1 protein, mousePhosphatidylinositol 3-KinasesReceptors, G-Protein-CoupledTOR Serine-Threonine Kinasesbile acidsGnRHmuricholic acidpubertyTGR5

Identifiers

PMID40920933
PMCPMC12452935

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.