Adrenal gland: Structure, function, and mechanisms of toxicity

The adrenal gland is one of the most common endocrine organs affected by ch emically induced Lesions. In the adrenal cortex, lesions are more frequent in the zona fasciculata and reticularis than in the zona glomerulosa. The a drenal cortex produces steroid hormones with a Iri-carbon nucleus following a series of hydroxylation reactions that occur in the mitochondria and end oplasmic reticulum. Toxic agents for the adrenal cortex include short-chain aliphatic compounds, lipidosis inducers, amphiphilic compounds. natural an d synthetic steroids, and chemicals that affect hydroxylation. Morphologic evaluation of cortical lesions provides insight into the sites of inhibitio n of steroidogenesis. The adrenal cortex response to injury is varied. Dege neration (vacuolar and granular), necrosis, and hemorrhage are common findi ngs of acute injury. In contrast, chronic reparative processes are typicall y atrophy, fibrosis, and nodular hyperplasia. Chemically induced proliferat ive lesions are uncommon in the adrenal cortex. The adrenal medulla contain s chromaffin cells (that produce epinephrine, norepinephrine. chromogranin, and neuropeptides) and ganglion cells. Proliferative lesions of the medull a are common in the rat and include diffuse or nodular hyperplasia and beni gn and malignant pheochromocytoma. Mechanisms of chromaffin cell proliferat ion in rats include excess growth hormone or prolactin, stimulation of chol inergic nerves, and diet-induced hypercalcemia. There often are species spe cificity and age dependence in the development of chemically induced adrena l lesions that should be considered when interpreting toxicity data.