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Drugs and Chemicals that Affect the Endocrine System

Department of Pharmacology, University of Texas Health Science Center, San Antonio, Texas, USA

The mammalian endocrine system is very dynamic, and undergoes frequent physiological fluctions due to diurnal variations and cyclical hormonal feedback systems. Both hormonal modulations and chemicall drug perturbations can affect the reproductive systems in males and females. An endocrine disrup-tor, a contemporary term that has been used to define an agent that disrupts the endocrine system, is a hormone or antihormone mimic that can modulate endocrine signaling pathways. Unfortunately, this terminology is confusing and ambiguous and fails to account for the ever-changing endogenous hormonal milieu. The endocrine system can be disrupted or modulated by many physiologic events (e.g., exercise, menstruation, pregnancy), by pharm acologic intervention (e.g., oral contraceptives, antithyroidal medication), and by nutritional states (e.g., iodine deficiencies, vitamin deficiencies and malnutrition). Seasonal changes (e.g., light and temperature) can also modulate endocrine events. Phytoestrogens and xenoestrogens (e.g., chlorinated pesticides) can also affect the dynamics of the endocrine system. Heavy metals and certain anti-cancer agents can interfere with testicular and ovarian function and may cause sterility. Several sites of action can be involved between a drug/chemical and the endocrine system, including the central nervous system, specific target organs or subpopulation of cells, hormone-transporting proteins, and xenobi-otic-m etabolizing enzymes in the liver. At the endocrine target organ level, mechanism(s) of action may involve competition for a cell receptor or affect non-receptor-mediated actions. Some drug!chemicals may act as hormone agonists (i.e., mimic) or conversely act as hormone antagonists (i.e., an antihormone); other agents may act as partial agonists or partial antagonists. Clearly, there are many internal and external factors that can modulate the endocrine system, yet the paracrine and autocrine regulation of specific target organs is finely regulated, and, importantly, is very resilient to drugl chemical perturbation.

Key Words: endocrine disruptors • environmental estrogens • estrogen = mimics • hormone antagonists • xenoestrogens

International Journal of Toxicology, Vol. 17, No. 2, 129-138 (1998)
DOI: 10.1080/109158198226666


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