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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
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Circadian clock disruption attenuated growth hormone(GH)-mediated signalling
Xintong Lyu1, Guohua Wang2, Zhuang Pi1
1Department of Pediatric Gastroenterology, The First Hospital of Jilin University, Changchun 130021, People's Republic of China.
General and Comparative Endocrinology
|November 27, 2020
Summary
The circadian clock regulates growth hormone (GH) activity. BMAL1 gene knockout mice show reduced GH signaling, indicating the clock
Area of Science:
- Chronobiology
- Endocrinology
- Molecular Biology
Background:
- The circadian molecular clock governs physiological rhythms.
- BMAL1 (brain and muscle arnt-like 1) is a key clock component.
- Circadian rhythms influence endocrine hormone secretion, including growth hormone (GH).
Purpose of the Study:
- To investigate the impact of circadian clock dysfunction on GH-mediated biological activities.
- To explore the molecular mechanisms underlying altered GH signaling in the absence of functional BMAL1.
Main Methods:
- Utilized BMAL1 gene knockout (BMAL-/-) mice model.
- Conducted in vivo studies assessing GH/GHR signaling pathways.
- Performed in vitro experiments using hepatocytes from BMAL-/- mice.
Main Results:
- GH-induced signaling was significantly down-regulated in BMAL-/- mice compared to controls.
- Reduced tyrosine phosphorylation of JAK-STAT signaling molecules was observed in vivo.
- Decreased GH/GHR-mediated signaling occurred in BMAL-/- hepatocytes.
- Increased expression of negative regulators (SOCS, protein phosphatases) was identified.
Conclusions:
- The circadian clock plays a crucial role in regulating the biological activities of growth hormone.
- Circadian clock dysfunction, specifically via BMAL1, impairs GH signaling.
- Upregulation of negative regulators may contribute to GH signaling downregulation.
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