Impact of peripubertal exposure to xenohormones on fat distribution and cytokines

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DESCRIPTION (provided by applicant): Puberty is a dynamic period which includes physiologic and biochemical changes, and may serve as a window of susceptibility for adult morbidity and mortality. For example, the majority of bone mineral content in females is deposited during the teen years, and the relationship between greater bone mineral density and breast cancer is established. Puberty is also a time of dramatic changes in body composition, with a rise in insulin resistance. The deposition of visceral fat is believed to increase the risk of metabolic complications of obesity, but little is known about factors in childhood that impact deposition of visceral fat. Certain environmental exposures (e.g., endocrine disruptors) impact body composition as well as timing of puberty. Studies in adults describe the relationship between breast cancer, obesity, insulin resistance, and adipokines. Leptin and pro-inflammatory cytokines induce aromatase activity and production of estrogen, as well as lead to insulin resistance, whereas adiponectin has an inverse relationship with breast cancer. We propose to utilize a unique existing cohort of racially and ethnically diverse girls who have been followed longitudinally from ages 6 and 7. These girls have had serial examinations over 2-4 years, including height, weight, and assessment of pubertal maturation, as well as urine biomarkers obtained at baseline. Our aims are: to evaluate the relationship between the accumulation of fat during pubertal maturation by race and timing of puberty, and exposure to phthalates and phytoestrogens; and evaluate the longitudinal relationship between the early exposures to endocrine disruptors, timing of pubertal maturation, development of insulin resistance, and changes in leptin and adiponectin. This proposal will incorporate anthropometric and maturation data from the previous longitudinal study with earlier biomarker data, to current assessments of: body composition, regional fat distribution, and bone density; fasting insulin, glucose, and lipid profile; the adipokines leptin and adiponectin; and an inflammatory marker, IL-6. Additionally, one subgroup has had insulin and glucose levels obtained at baseline, and we propose to add analyses of stored sera from that time for analysis of leptin and adiponectin levels. This will allow us to better understand the relationships between timing of puberty, exposures to endocrine disruptors, pubertal body composition changes, and underlying mechanisms of insulin resistance with obesity and the metabolic syndrome. This study may help to inform interventions for prevention of breast cancer and the metabolic consequences of obesity. PUBLIC HEALTH RELEVANCE: The cohort of girls in this protocol have been followed longitudinally from ages 6 and 7 with physical examinations and measurement of environmental and dietary exposures. The additional studies in this proposal will allow the investigators to observe changes in body composition, bone content, and biochemical processes during puberty, a crucial period of growth and development.