Endocrine System

The endocrine glands are an important group of organs that are susceptible to chemical-induced changes that occur in short- and long-term preclinical toxicology studies. It is important to differentiate spontaneous and stress-related changes from compound-induced effects. There are multiple examples of drugs that are approved for human use that have been associated with degenerative or neoplastic changes in the endocrine glands of laboratory animals, but the weight of evidence regarding the pathogenesis and mode of action has demonstrated a lack of relevance for humans. The mode of action of chemicals on the toxicology of the endocrine glands can be direct or indirect. Therefore, studies on the modes of action require knowledge and experimental interrogation of physiological control and feedback mechanisms, hormone distribution and receptors on diverse target cells, the primary endocrine cells, and peripheral metabolism and excretion of hormones. In addition, there is a significant interspecies difference in the physiology and pathology of the endocrine glands, which makes it imperative to understand the mode of action of chemicals in order to compare preclinical toxicology findings in different species and predict human relevance. This chapter reviews the pathophysiology of the endocrine glands in the species typically used for preclinical toxicology studies and includes toxicologic mechanisms, classic examples of chemical-induced changes and their modes of action, and spontaneous diseases.