2002 Progress Report: Neuroendocrine Mechanisms of Environmental Toxicants: PCBs and Pesticides

EPA Grant Number: R827039C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R827039
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Mount Sinai Center for Children's Environmental Health and Disease Prevention Research
Center Director: Wolff, Mary S.
Title: Neuroendocrine Mechanisms of Environmental Toxicants: PCBs and Pesticides
Investigators: Gore, Andrea , Wolff, Mary S.
Institution: Mount Sinai School of Medicine
EPA Project Officer: Callan, Richard
Project Period: August 1, 1998 through July 31, 2003 (Extended to July 31, 2004)
Project Period Covered by this Report: August 1, 2001 through July 31, 2002
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Health

Objective:

Our final research project is an experimental neurodevelopmental study that is intended to elucidate the mechanism by which PCBs and other environmental agents adversely affect neuroendocrine and early reproductive development. Using a female rat model, this project will examine the role of developing GnRH neurons and their neuronal and glial inputs in the neuroendocrine dysfunctions that occur in organisms exposed to environmental toxicants.

Progress Summary:

During the past year, we have completed the studies using the GT1-7 cell line (Specific Aim 4). In those experiments, effects of toxicants (Aroclor 1221, Aroclor 1254, chlorpyrifos and methoxychlor) were tested on GnRH gene expression and release, and on GT1-7 cell morphology. In general, Aroclor 1221 stimulated GnRH gene expression and neurite outgrowth in the GT1-7 cells, while Aroclor 1254 inhibited these parameters. Interestingly, these effects are consistent with published reports demonstrating stimulatory effects of Aroclor 1221, and inhibitory effects of Aroclor 1254, in animal studies. For the pesticides, chlorpyrifos and methoxychlor had essentially similar effects, stimulating GnRH gene expression at low doses, and inhibiting it in high doses. The finding that chlorpyrifos has direct effects on this GnRH cell line is particularly interesting as little is known about its effects as an endocrine-disrupting chemical, and these findings provide support for such a role. The results of these studies have been accepted for publication in two peer-reviewed journals. The citations are below.

I have also made further progress on the in vivo studies and have prepared two manuscripts for publications (Aims 1-3). For these experiments, we have been testing the same PCBs and pesticides described above for the GT1-7 cells on reproductive development in rats. For the PCBs, we have observed significant stimulatory effects of Aroclor 1221, but no effect of Aroclor 1254, on GnRH gene expression. The stimulatory effect of Aroclor 1221 is consistent with that reported in the literature, and suggests that the GnRH system represents a mechanism by which estrogenic PCBs such as Aroclor 1221 exert their effects. Effects of chlorpyrifos were limited to somatic development (delay in body weight). We have written two manuscripts on this project and expect to submit them shortly (see below).

Because all of these animal studies involved exposing rats to prenatal or early postnatal toxicants, we have followed up with another acute study in which we have administered PCBs to neonatal pups (6 days old) and assayed the effects one day later. We found in preliminary studies that Aroclor 1221 inhibited GnRH gene expression in female pups. This effect is opposite to the long-term effects of Aroclor 1221 seen when animals are examined as adults. Thus, the acute and the long-term effects of PCBs are quite different on the reproductive neuroendocrine axis.

Finally, based on the recommendation of the External Advisory Committee to test effects of combinations of PCBs on GnRH gene expression, we have performed an experiment to analyze interactions of Aroclor 1221 and Aroclor 1254. The experiment has been completed and we are nearly done with the data analysis of this study. The results will be reported in the next progress report.

Supplemental Keywords:

RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Toxics, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, Environmental Chemistry, Health Risk Assessment, Exposure, Epidemiology, pesticides, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Biochemistry, Physical Processes, Children's Health, genetic susceptability, Risk Assessment, health effects, pesticide exposure, sensitive populations, health risks, PCBs, biological response, neurodevelopment, children, Human Health Risk Assessment, neurotoxicity, human exposure, pesticide residues, assessment of exposure, growth and development, neurodevelopmental toxicity, exposure pathways, harmful environmental agents, environmental health hazard, dietary exposure, growth & development, developmental disorders, exposure assessment, neurological development

Progress and Final Reports:

Original Abstract
  • 1999
  • 2000 Progress Report
  • 2001
  • 2003
  • Final

  • Main Center Abstract and Reports:

    R827039    Mount Sinai Center for Children's Environmental Health and Disease Prevention Research

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R827039C001 Growing Up Healthy in East Harlem
    R827039C002 Exposure to Indoor Pesticides and PCBs and their Effects on Growth and Neurodevelopment in Urban Children
    R827039C003 Genetics of Chlorpyrifos Risk in Minority Populations
    R827039C004 Prenatal PCB Exposure and Neurodevelopmental Outcomes in Adolescence and Adulthood
    R827039C005 Neuroendocrine Mechanisms of Environmental Toxicants: PCBs and Pesticides