Project 171078

Endogenous hormones as modulators and targets of polycyclic aromatic hydrocarbon action

171078

Endogenous hormones as modulators and targets of polycyclic aromatic hydrocarbon action

$685,110
Project Information
Study Type: Other Mechanistic_Study
Therapeutic Area: Endocrinology
Research Theme: Biomedical
Disease Area: cancer, developmental and reproductive disorders
Data Type: Canadian
Institution & Funding
Principal Investigator(s): Riddick, David S
Institution: University of Toronto
CIHR Institute: Population and Public Health
Program: Operating Grant
Peer Review Committee: Pharmaceutical Sciences
Competition Year: 2008
Term: 5 yrs 0 mth
Abstract Summary

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 other combustion processes. We are studying how hormones produced by the pituitary and adrenal glands control the sensitivity of an organism to the toxic effects of aromatic hydrocarbons and how these chemicals interfere with the normal functions of pituitary hormones. In particular, pituitary growth hormone plays a key role in controlling liver enzymes known as cytochromes P450, which are crucial in the conversion of drugs, contaminants, and hormones into forms that can be eliminated from the body. Increases or decreases in cytochromes P450 are sensitive indicators of aromatic hydrocarbon exposure.

Research Characteristics

This project includes the following research characteristics:

Environmental Health
Knowledge Translation Focus
Biomarker Endpoints
Study Justification

"We are studying how hormones produced by the pituitary and adrenal glands control the sensitivity of an organism to the toxic effects of aromatic hydrocarbons and how these chemicals interfere with the normal functions of pituitary hormones."

Novelty Statement

"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."

Methodology Innovation

investigating the mechanisms by which aromatic hydrocarbons interfere with the endocrine system, with a focus on pituitary and adrenal hormones and cytochrome P450 enzymes

Keywords
Aryl Hydrocarbon Receptor Cytochrome P450 Gene Expression Halogenated Aromatic Hydrocarbons Hormonal Regulation Polycyclic Aromatic Hydrocarbons