Environmental estrogens and obesity.
Many chemicals in the environment, in particular those with estrogenic activity, can disrupt the programming of endocrine signaling pathways that are established during development and result in adverse consequences that may not be apparent until much later in life. Most recently, obesity and diabetes join the growing list of adverse consequences that have been associated with developmental exposure to environmental estrogens during critical stages of differentiation. These diseases are quickly becoming significant public health issues and are fast reaching epidemic proportions worldwide. In this review, we summarize the literature from experimental animal studies documenting an association of environmental estrogens and the development of obesity, and further describe an animal model of exposure to diethylstilbestrol (DES) that has proven useful in studying mechanisms involved in abnormal programming of various differentiating estrogen-target tissues. Other examples of environmental estrogens including the phytoestrogen genistein and the environmental contaminant Bisphenol A are also discussed. Together, these data suggest new targets (i.e., adipocyte differentiation and molecular mechanisms involved in weight homeostasis) for abnormal programming by estrogenic chemicals, and provide evidence that support the scientific hypothesis termed "the developmental origins of adult disease". The proposal of an association of environmental estrogens with obesity and diabetes expands the focus on the diseases from intervention/treatment to include prevention/avoidance of chemical modifiers especially during critical windows of development.
Developmental Endocrinology and Endocrine Disruptor Section, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, United States. newbold1@niehs.nih.gov
Retha R
RR
Newbold
Elizabeth
E
Padilla-Banks
Wendy N
WN
Jefferson
D000818:Animals; D001835:Body Weight; D004054:Diethylstilbestrol / Q000378:metabolism; D004195:Disease Models, Animal; D052244:Endocrine Disruptors / Q000378:metabolism*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000378:metabolism*; D004968:Estrogens, Non-Steroidal / Q000378:metabolism; D006801:Humans; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology
D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D004054:Diethylstilbestrol