Extra-Adrenal Glucocorticoid Synthesis in Mucosal Tissues and Its Implication in Mucosal Immune Homeostasis and Tumor Development

Kostadinova, Feodora Ivanova; Hostettler, Nina; Brunner, Thomas

doi:10.5772/52788

Cited by 1 publication

(1 citation statement)

References 125 publications

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“…[68][69][70][71] For local immunomodulation, extra-adrenal cortisol synthesis has been found in various tissues such as the skin and intestine. [72][73][74] Thus, it is likely that mc2r homozygous mutants still have certain levels of cortisol. However, HPI axis activation via mc2r appears to be indispensable in rapid locomotor response to acute stressors based on our findings that decreased locomotor phenotypes of mc2r are reproduced in two distinct stressors (light illumination vs salinity changes) mediated through different biological processes (visual system vs osmoregulation).…”

Section: Whole-body Cortisol Levels Are Congruent With Locomotor Rementioning

confidence: 99%

Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response

Lee

Schwab

Sigafoos

et al. 2019

Genes Brain and Behavior

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When vertebrates face acute stressors, their bodies rapidly undergo a repertoire of physiological and behavioral adaptations, which is termed the stress response. Rapid changes in heart rate and blood glucose levels occur via the interaction of glucocorticoids and their cognate receptors following hypothalamic‐pituitary‐adrenal axis activation. These physiological changes are observed within minutes of encountering a stressor and the rapid time domain rules out genomic responses that require gene expression changes. Although behavioral changes corresponding to physiological changes are commonly observed, it is not clearly understood to what extent hypothalamic‐pituitary‐adrenal axis activation dictates adaptive behavior. We hypothesized that rapid locomotor response to acute stressors in zebrafish requires hypothalamic‐pituitary‐interrenal (HPI) axis activation. In teleost fish, interrenal cells are functionally homologous to the adrenocortical layer. We derived eight frameshift mutants in genes involved in HPI axis function: two mutants in exon 2 of mc2r (adrenocorticotropic hormone receptor), five in exon 2 or 5 of nr3c1 (glucocorticoid receptor [GR]) and two in exon 2 of nr3c2 (mineralocorticoid receptor [MR]). Exposing larval zebrafish to mild environmental stressors, acute changes in salinity or light illumination, results in a rapid locomotor response. We show that this locomotor response requires a functioning HPI axis via the action of mc2r and the canonical GR encoded by nr3c1 gene, but not MR ( nr3c2 ). Our rapid behavioral assay paradigm based on HPI axis biology can be used to screen for genetic and environmental modifiers of the hypothalamic‐pituitary‐adrenal axis and to investigate the effects of corticosteroids and their cognate receptor interactions on behavior.

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Section: Whole-body Cortisol Levels Are Congruent With Locomotor Rementioning

confidence: 99%

Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response

Lee

Schwab

Sigafoos

et al. 2019

Genes Brain and Behavior

View full text Add to dashboard Cite

show abstract

Extra-Adrenal Glucocorticoid Synthesis in Mucosal Tissues and Its Implication in Mucosal Immune Homeostasis and Tumor Development

Cited by 1 publication

References 125 publications

Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response

Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response

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