Proliferative lesions of the medulla are common in the rat and include diffuse or nodular hyperplasia and benign and malignant pheochromocytoma. The adrenal medulla contains chromaffin cells (that produce epinephrine, norepinephrine, chromogranin, and neuropeptides) and ganglion cells. Chemically induced proliferative lesions are uncommon in the adrenal cortex. In contrast, chronic reparative processes are typically atrophy, fibrosis, and nodular hyperplasia. Degeneration (vacuolar and granular), necrosis, and hemorrhage are common findings of acute injury. The adrenal cortex response to injury is varied. Morphologic evaluation of cortical lesions provides insight into the sites of inhibition of steroidogenesis. Toxic agents for the adrenal cortex include short-chain aliphatic compounds, lipidosis inducers, amphiphilic compounds, natural and synthetic steroids, and chemicals that affect hydroxylation. The adrenal cortex produces steroid hormones with a 17-carbon nucleus following a series of hydroxylation reactions that occur in the mitochondria and endoplasmic reticulum. In the adrenal cortex, lesions are more frequent in the zona fasciculata and reticularis than in the zona glomerulosa. The adrenal gland is one of the most common endocrine organs affected by chemically induced lesions.
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