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Secondary adrenal insufficiency occurs because the adrenal glands are not told by the pituitary gland or hypothalamus in the brain, via the hormone ACTH, to make enough hormones

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However, under oxidative stress, oxidative modification of cysteine residues in Keap1 causes conformational changes that weaken its binding to Nrf2, allowing Nrf2 to dissociate from Keap-1 and rapidly translocate to the nucleus