4.09 – Toxic Responses of the Adrenal Cortex☆

摘要: The adrenal gland is reported to be the most common toxicological target organ within endocrine system. It a vital with universal steroidogenic capability and there are well-described cases of human drug-induced adrenocortical toxicity, typically resulting from unpredicted enzyme inhibition. Adrenal hypertrophy/adrenocortical cellular hypertrophy findings in toxicity studies also often incorrectly attributed “stress”: these should not stress unless clear evidence that cortex functional. This article reviews endocrinology hypothalamo-pituitary–adrenocortical system steroidogenesis identifying many potential physiological molecular targets for factors predisposing toxic insult. In vivo assessment models strategies reviewed including species differences effects age gender. need proper examination mechanistic cause (which usually results excess adrenocorticotrophic hormone (ACTH) secretion) discussed terms comparison more benign ACTH drive due sinister effect inhibition insufficiency which loss glucocorticoids, reduced feedback inhibition, unrestrained stimulation adrenal. In vitro use cell lines both screening mechanism elucidation discussed. Examples mechanisms responses given. focus on as but glucocorticoid modulation response insult discussed: functional activation one after infection or injury, insult, action glucocorticoids can profoundly alter Human dysfunction discussed, point view drugs known (e.g., etomidate, aminoglutethimide, synthetic steroids all have different mechanisms) means consequences disruption specific important health disease inferred. Finally, environmental increased awareness concern through estrogenic survival fitness environmentally sentinel such fish birds reviewed.