Highlights
Anti-Müllerian Hormone Signalling Sustains Circadian Homeostasis
Prominent daily physiological and behavioural rhythms are orchestrated by self-sustained biological oscillators called circadian clocks, which have an internally driven 24-hour day–night rhythm and are controlled by a transcriptional autoregulatory feedback loop involving multiple clock genes. Clock function arises from the molecular oscillator within each cell and extends anatomically to form an organism-wide system. While the molecular components of circadian clock are well characterized, the mechanisms by which long-term circadian homeostasis and oscillation are achieved throughout complex systems and anatomical regions are poorly understood.
Recently, a collaborative study led by Prof. MIE Jie and Prof. GUI Jianfang from Institute of Hydrobiology (IHB) of the Chinese Academy of Sciences, along with Prof. XIAO Rui from Wuhan University, has revealed that the endocrine factor anti-Müllerian hormone (Amh) ensures precise gating of the major output pathways of circadian information, thereby maintaining rhythm coherence and circadian homoeostasis at both tissue and systemic levels. This study was published in Nature Communications.
In this study, the researchers reported that Amh signalling is essential for sustaining robust circadian oscillations of molecular clocks and hormonal and behavioural rhythms. Amh primarily acts on somatotropes and gonadotropes in the pituitary. Moreover, single-cell RNA sequencing further revealed the lineage-specific regulation of the pituitary circadian clock by Amh.
To elucidate the molecular mechanisms by which Amh regulates circadian rhythms, the researchers conducted a series of in vivo and in vitro experiments, confirming that the Bmpr2a protein serves as the type II receptor for Amh. Knockout of bmpr2a results in disruption of the circadian clock and behavioural rhythms, which are similar to those of amh mutants.
Further analysis revealed that phospho-Smad1/5/9 (P-Smad1/5/9) binds to most clock genes in wild-type pituitary, whereas such binding is significantly reduced in both amh and bmpr2a mutants. Moreover, the researchers found that Amh-induced effect on clock gene expression can be abolished by blocking Smad1/5/9 phosphorylation and bmpr2a knockout.
Mechanistically, Amh binds to its receptors, Bmpr2a/Bmpr1bb, which in turn activate Smad1/5/9 by phosphorylation and promote circadian gene expression through multiple evolutionarily conserved clock-controlled elements.
These findings reveal a novel molecular mechanism of endocrine-clock crosstalk, offering profound insights into the neuroendocrine regulation of vertebrate circadian rhythms and long-term homeostasis. It also provides a theoretical basis for the genetic improvement of fish economic traits such as growth and stress resistance.
(Online: 10 May 2025)
(Editor: MA Yun)