Epigenetic regulation of glucocorticoid receptor and infantile spasms.

Abstract

IS is one of the few seizure syndromes that can be alleviated by adrenocorticotropic hormone (ACTH) or glucocorticoids (GCs) that are considered effective drugs of choice. This indicates that, indeed, IS may be fundamentally different from most other seizure disorders owing to the dysregulation of the hypothalamic-hypophysial-adrenal axis. GCs have multiple critical effects on fetal development, especially in normal brain development. Most glucocorticoid effects are mediated by the glucocorticoid receptor (GR), a steroid-activated nuclear receptor that translocates to the nucleus upon binding to cortisol. In the nucleus, GR targets genes related to neuronal metabolism and plasticity. The GR has also been characterized as a critical checkpoint in the delicate hormonal control of energy homeostasis. Recent studies suggest a possible correlation between prenatal stress and the onset of infantile spasms. In this paper, we propose a hypothesis that connects the adverse events in early life with the onset of IS through methylation of the GR gene, which is an epigenetic mechanism.

• Authors: Guang Yang, Li-Ping Zou, Jing Wang, Ying-Xue Ding
• Journal: Medical hypotheses (Med Hypotheses) Vol. 76 Issue 2 Pg. 187-9 (Feb 2011) ISSN: 1532-2777 [Electronic] United States
• PMID: 20943324 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Glucocorticoids
• Receptors, Glucocorticoid
• Adrenocorticotropic Hormone

Topics

• Adrenocorticotropic Hormone (metabolism)
• Animals
• Cell Nucleus (metabolism)
• Epigenesis, Genetic
• Glucocorticoids (metabolism)
• Humans
• Infant, Newborn
• Methylation
• Models, Biological
• Rats
• Receptors, Glucocorticoid (genetics, metabolism)
• Spasms, Infantile (metabolism)