Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress.

摘要: The adrenal glucocorticoids and catecholamines comprise a frontline of defense for mammalian species under conditions which threaten homeostasis (conditions commonly referred to as stress). Glucocorticoids represent the end product hypothalamic-pituitary-adrenal (HPA) axis along with serve mobilize production distribution energy substrates during stress. increased secretion pituitary-adrenal hormones in response stress is stimulated by release corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP) from neurons nucleus paraventricularis. In this way, neural signal associated stressor transduced into set endocrine sympathetic responses. development HPA stressful stimuli altered early environmental events. Animals exposed short periods infantile stimulation or handling show decreased responsivity stress, whereas maternal separation, physical trauma endotoxin administration enhance all cases, these effects persist throughout life animal are accompanied hypothalamic levels mRNAs CRH often AVP. inhibitory regulation synthesis ACTH releasing factors achieved, part, through negative feedback loop whereby circulating act at various sites decrease AVP gene expression. Such initiated via an interaction between steroid intracellular receptor (either mineralocorticoid glucocorticoid receptor). We have found that manipulations regulate expression hippocampus frontal cortex, regions been strongly implicated negative-feedback synthesis. When differences density transiently reversed, so too those responses Taken together, our findings indicate postnatal environment alters differentiation hippocampal neurons. This effect involves rate expression, resulting changes sensitivity system on Changes levels, turn, determine subsequent stressors; factor Thus, can contribute substantially stable individual stimuli. These data provide examples programming systems. One major objective research understand how such occurs within brain.