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Endocrine Disruption in Adolescence

EPA Grant Number: R827404
Title: Endocrine Disruption in Adolescence
Investigators: Golub, Mari S. , Gershwin, M. Eric , Hendrickx, Andrew G.
Institution: University of California - Davis
EPA Project Officer: Fields, Nigel
Project Period: September 1, 1999 through August 31, 2002 (Extended to August 31, 2003)
Project Amount: $670,805
RFA: Endocrine Disruptors (1999)
Research Category: Endocrine Disruptors

Description:

Endocrine disruption can interfere with the organizational role of steroid hormones at critical developmental periods. We propose to investigate the effects of the estrogenic agent methoxychlor (MXC) on adolescence by using a nonhuman primate model that adequately represents the prolonged and complex adolescent period of humans. Results will help determine whether MXC generally alters the onset and timecourse of adolescent maturation through actions at hypothalamic regulatory sites, or acts more directly and discretely on tissues that mature under the influence of estrogen such as bone, brain, and immune systems, as well as the reproductive system.

Approach:

MXC has been selected as a valuable model endocrine disrupting agent for our purposes because it is a currently used pesticide and potential environmental contaminant, and because it has been studied for its effects on puberty in rodents. The following endpoints will be evaluated:

  1. precocious puberty, abnormal reproductive tract morphology and histology, ovarian function
  2. changes in lymphocyte populations and cytotoxic activity
  3. maturational characteristics of brain electrical activity
  4. skeletal growth and mineralization
MXC will be administered orally to female rhesus monkeys at 2 dose levels from 24 mos of age (approximately equivalent to 8 y of age in humans) to 39 mos of age (14 y in humans). After dosing, the young monkeys will be allowed to recover until the age of full sexual maturation (45 months, 16 y in humans) and then examined for successful completion of adolescence in terms of growth, ovarian cyclicity, reproductive tract morphology and histology, brain development and immune function. Noninvasive methods such as brain EEG, bone scans, urine hormone measures, colposcopy, and characterization of lymphocyte populations in peripheral blood samples will be used. Diethyl stilbestrol (DES) will serve as a positive control. The project period is 3 years.

Expected Results:

This project is intended to respond to USEPA's interest in endocrine disruptor effects on reproductive, immune, and central nervous systems. It will provide information on adolescents as a sensitive population for endocrine disruption resulting in subfertility in adulthood, impairment in function of late maturing brain areas, enhanced susceptibility to pathogens encountered by young adults, and postmenopausal osteoporosis.

Publications and Presentations:

Publications have been submitted on this project: View all 16 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 4 journal articles for this project

Supplemental Keywords:

health effects, sensitive populations, children, primatology, risk assessment, , Scientific Discipline, Health, RFA, Susceptibility/Sensitive Population/Genetic Susceptibility, Endocrine Disruptors - Environmental Exposure & Risk, Biology, Risk Assessments, genetic susceptability, Health Risk Assessment, endocrine disruptors, Epidemiology, Children's Health, Environmental Chemistry, Endocrine Disruptors - Human Health, environmentally caused disease, environmental hazard exposures, endocrine disruption, endocrine disrupting chemicals, puberty, environmental toxicant, Methoxychlor, assessment of exposure, harmful environmental agents, hypothalamus, immune system response, toxics, reproductive processes, sensitive populations, estrogen receptors, steroid, children, hormone production, Lymphocytes, cytotoxic, age dependent response, adolescence, diethyl stilbestrol, human exposure

Progress and Final Reports:
2000 Progress Report
Final Report

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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