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Epigenetics/Programming in the HPA Axis

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The hypothalamic‐pituitary‐adrenal axis provides physiological adaptations to various environmental stimuli in mammals. These stimuli including maternal care, diet, immune challenge, stress, and others have the potential to stably modify or program the functioning of the HPA axis when experienced early in life or at later critical stages of development. Epigenetic mechanisms mediate the biological embedding of environmental stimuli or conditions. These changes are influenced by the genotype and both, environment and genotype contribute to the development of a specific phenotype with regard to the stress response that might be more susceptible or resilient to the development of mental conditions. The effects of stress might be a result of cumulative stress or a mismatch between the environments experienced early in life versus the conditions much later. These effects including the associated epigenetic modifications are potentially reversible. © 2016 American Physiological Society. Compr Physiol 6:87‐110, 2016.

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Figure 1. Figure 1. Schematic illustration of the glucocorticoid receptor genes (NR3C1) in rat und human. Open boxes represent first exons. A single first exon is spliced onto exon 2 together with exon 3 to 9 (closed boxes). Black boxes represent nonspliced exons whereas grey boxes represent spliced exons at the 3′ primed end of the gene. The corresponding exons 1‐7 (rat) and 1‐F (human) are connected by doted lines. The human gene contains at least 10 first exons; the rat gene contains 11 first exons. Adapted, with permission, from ().

Figure 1. Schematic illustration of the glucocorticoid receptor genes (NR3C1) in rat und human. Open boxes represent first exons. A single first exon is spliced onto exon 2 together with exon 3 to 9 (closed boxes). Black boxes represent nonspliced exons whereas grey boxes represent spliced exons at the 3′ primed end of the gene. The corresponding exons 1‐7 (rat) and 1‐F (human) are connected by doted lines. The human gene contains at least 10 first exons; the rat gene contains 11 first exons. Adapted, with permission, from ().
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Jan P. Buschdorf, Michael J. Meaney. Epigenetics/Programming in the HPA Axis. Compr Physiol 2015, 6: 87-110. doi: 10.1002/cphy.c140027