Grant: Operating Grant

Hormones are the chemical messengers of the endocrine system that regulate the body's normal functions, and they are also critical in playing adaptive roles in response to events outside the body. Some pollutants found in our environment can interfere with or disrupt the normal body functions that are controlled by hormones. These agents are referred to as "endocrine disruptors". Disruption of normal hormone pathways by environmental contaminants can contribute to several adverse or toxic effects, including cancer as well as alterations in growth, development, and reproductive function. Our goal is to understand the mechanisms by which environmental contaminants interfere with the endocrine system. In this way, we will have a clearer appreciation of why exposure to such chemicals can be detrimental and how we can prevent the adverse effects of chemical exposure. Our focus is on environmental contaminants known as aromatic hydrocarbons. This chemical class includes dioxins and polychlorinated biphenyls (PCBs), as well as components of cigarette smoke and automobile exhaust. In this specific proposal, we are studying how these chemicals interfere with the normal functions of growth hormone, an important molecule produced in the pituitary gland. Pituitary growth hormone plays a key role in controlling liver enzymes known as cytochromes P450, which are critical in the conversion of drugs, contaminants, and hormones into forms that can be eliminated from the body. Increases or decreases in the levels of cytochromes P450 are sensitive indicators of aromatic hydrocarbon exposure.