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Glucocorticoid-Mediated Developmental Programming of Vertebrate Stress Responsivity
Ian M Gans1,2, James A Coffman1,2
1MDI Biological Laboratory, Salisbury Cove, ME, United States.
Frontiers in Physiology
|January 7, 2022
Summary
Glucocorticoids maintain homeostasis by activating nuclear receptors like the Glucocorticoid Receptor (GR). Chronic stress alters GR signaling dynamics, potentially programming long-term health and disease susceptibility.
Area of Science:
- Endocrinology
- Neuroscience
- Molecular Biology
Background:
- Glucocorticoids are vital steroid hormones for homeostasis, regulated by the hypothalamus-pituitary-adrenal axis.
- Glucocorticoid and Mineralocorticoid Receptors (MR and GR) mediate glucocorticoid actions.
- GR signaling dynamics are crucial for stress response and adaptation.
Purpose of the Study:
- Investigate the glucocorticoid-responsive gene regulatory network.
- Identify key regulators in stress system programming.
- Understand the role of KLF9 in GR signaling dynamics.
Main Methods:
- Analysis of glucocorticoid signaling pathways.
- Study of gene regulation by GR.
- Examination of the role of target genes like FKBP5 and KLF9.
Main Results:
- GR transduces dynamic glucocorticoid signals related to circadian rhythms and stress.
- Chronic stress can lead to altered GR signaling dynamics and increased allostatic load.
- KLF9 acts as a feedforward regulator of GR signaling, influencing cellular glucocorticoid responsiveness.
Conclusions:
- GR signaling dynamics are critical for physiological adaptation and stress responsivity.
- Early life stress can program the stress system via altered gene regulatory networks.
- KLF9 emerges as a key regulator in the glucocorticoid response network, potentially involved in developmental programming.
Keywords:
Klf9adaptiveallostasiscortisoldynamicsearly life stressgene regulationglucocorticoid receptorMore Related Videos
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