Jump to main content.

Reproductive Toxicology Division

Reproductive Toxicology Division

Neuroendocrine Function Team (NEF)

Overview

Objectives of the Neuroendocrine Function team include characterizing the range of environmental agents that alter luteinizing hormone (LH) secretion, identifying central nervous system (CNS) mechanisms involved in their mode of action, and determining key events necessary for altered reproductive function. An important question is whether a common mechanism of action exists across test species which can be extrapolated to humans. Work thus far has demonstrated that xenobiotics can alter the regulation of LH. In addition to evaluating the effect of a single chemical, this group is also examining the effect of combined treatments with those xenobiotics known to alter LH secretion to determine whether they are dose additive.

The team’s research is focused on the following Long-Term Goal (LTG) in EPA’s Multi-Year Plans (MYP):

*Senior Environmental Employment Program

NEF Team Projects

Identifying How Environmental Chemicals Affect LH Secretion: A “Systems Biology” Approach

Contact: Jerome Goldman

The primary focus of this project is to investigate the mode and mechanism of action through which individual environmental agents affect the neuroendocrine control of reproduction. Research objectives include identifying environmental chemicals that modify the ovulatory surge of luteinizing hormone (LH), determining whether the site of action is at the level of the pituitary or hypothalamus, and assessing to what extent the ovary and ovulation are affected. A large part of this project’s research is the use of various protocols to (1) determine if ovarian function is impaired by a chemical; and (2) to investigate the nature and target site of the impairment’s origin. Importantly, the determination of the mechanism of chemical action is critical for the extrapolation of results from test species to humans.

Changes in the Hypothalamic-Pituitary-Adrenal Axis: Impact on the Control of Reproductive Function

Contact: Susan Laws

The primary question addressed by this project is whether disruption of hypothalamic-pituitary-adrenal (HPA) axis function plays a role in observed, toxicant-induced alterations in gonadal and reproductive function. A variety of research approaches are used to identify the cellular mechanisms by which environmental chemicals alter the hormonal regulation of the HPA axis. An important objective of this work is to determine whether effects on the HPA and the hypothalamic-pituitary-gonadal (HPG) axes are mediated through central nervous system modulation of hypothalamic releasing factor secretion. These studies address complex questions concerning alterations in gonadal and adrenal steroidogenesis and the potential interplay between the HPA and HPG axes during chemically-induced changes in reproductive function.

Characterization of Adverse Outcomes Following Disruption of the Neuroendocrine Control of Pituitary Function

Contact: Tammy Stoker

The purpose of this project is to evaluate adverse reproductive, developmental and functional outcomes that occur following disruption of luteinizing hormone (LH) secretion and to identify the most appropriate animal model to study these alterations. Certain investigations have focused on the evaluation of chemically-induced disruption of hypothalamic control mechanisms involved in impaired pregnancy outcome. Other work has involved the investigation of the role of chemically-induced alteration of LH secretion in impaired pubertal development or pregnancy maintenance. An overarching aim of this project is the determination of the chemically-induced physiological changes that develop prior to the onset of adverse outcomes in order to provide a better understanding of the degree of homology between rat and human leading to an estimation of the probability that such an outcome would occur in the human population.

Recent Publications

Publications are listed in reverse chronological order. The names of current RTD employees are in bold.
Cooper RL, Laws SC, Das PC, Narotsky MG, Goldman JM, Tyrey EL, Stoker TE. 2007. Atrazine and reproductive function: Mode and mechanism of action studies. Birth Defects Research (Part B) 80:98-112. Abstract

Goldman JM, Murr AE, Cooper RL. 2007. The rodent estrous cycle: Characterization of vaginal cytology and its utility in toxicological studies. Birth Defects Res B Dev Reprod Toxicol. 80:84-97. Abstract

Stoker TE, Cooper RL. 2007. Distribution of 14c-atrazine following an acute lactational exposure in the Wistar rat. Reprod Toxicol. 8023:607-610. Abstract

Goldman JM, Murr AE, Buckalew AR, Ferrell JM, Cooper RL. 2007. Moderating influence of the drinking water disinfection by-product dibromoacetic acid on a dithiocarbamate-induced suppression of the luteinizing hormone surge in female rats. Reprod Toxicol. 23:541-549. Abstract

Bielmeier SR, Murr AE, Best DS, Harrison RA, Pegram RA, Goldman JM, Narotsky MG. 2007. Effects of bromodichloromethane on ex vivo and in vitro luteal function and bromodichloromethane tissue dosimetry in the pregnant F344 rat. Toxicol In Vitro. 21:919-928. Abstract

Goldman JM, Cooper RL, Murr AE. 2007. Reproductive functions and hypothalamic catecholamines in response to the soil fumigant metam sodium: Adaptations to extended exposures. Neurotoxicol Teratol. 29:368-376. Abstract

Cooper RL, Laws SC, Das PC, Wong JS, Narotsky MG, Goldman JM, Stoker TE. 2007. Atrazine and reproductive function: mode and mechanism of action studies. Birth Defects Res B Dev Reprod Toxicol. 80(2):98-112. Abstract

Laws SC, Yavanhxay S, Cooper RL, Eldridge J. 2006. Nature of the Binding Interaction for 50 Structurally Diverse Chemicals with Rat Estrogen Receptors. Toxicol Sci. 94:46-56. Abstract

Murr AS, Goldman JM. 2005. Twenty week exposures to the drinking water disinfection by-product dibromoacetic acid: reproductive cyclicity and steroid concentrations in the female Sprague-Dawley rat. Reprod Toxicol. 20:73-80. Abstract

Stoker TE, Cooper RL, Lambright CS, Wilson VS, Furr JR, Gray LE. 2005. In vivo and in vitro anti-androgenic effects of DE-71, a commercial polybrominated diphenyl ether (PBDE) mixture. Toxicol Appl Pharmacol. 207:78-88. Abstract

Stoker TE, Perreault SD, Bremser K, Marshall RS, Murr AS, Cooper RL. 2005. Acute exposure to molinate alters neuroendocrine control of ovulation in the rat. Toxicol Sci. 84:38-48. Abstract

Goldman JM, Laws SC, Cooper RL. 2004. Assessment of toxicant-induced alterations in ovarian steroidogenesis: A methodological overview. In: Ovarian Toxicology. Ed.: P. Hoyer, Taylor & Francis, New York. pp. 202-222.

Goldman JM, Murr AS, Buckalew AR, Schmid JE, Abbott BD. 2004. Methoxychlor-induced alterations in the histological expression of angiogenic factors in pituitary and uterus. J Mol Histol. 35:363-375. Abstract

Cooper RL, Laws SC, Narotsky MG, Goldman JM, Stoker TE. (2004). Hormonal control of ovarian function following chlorotriazine exposure: Effect on reproductive function and mammary gland tumor development. In: Ovarian Toxicology. Ed.: P. Hoyer, Taylor & Francis, New York. pp. 94-113.

Stoker TE, Jeffay SC, Zucker RM, Cooper RL, Perreault SD. 2003. Abnormal fertilization is responsible for reduced fecundity following thiram-induced ovulatory delay in the rat. Biol Reprod. 68:2142-2149. Abstract

Goldman JM, Murr AS. 2003. Dibromoacetic acid-induced elevations in circulating estradiol: effects in both cycling and ovariectomized/steroid-primed female rats. Reprod Toxicol. 17:585-592. Abstract

Wery N, Narotsky MG, Pacico N, Kavlock RJ, Picard JJ, Gofflot F. 2003. Defects in cervical vertebrae in boric acid-exposed rat embryos are associated with anterior shifts of HOX gene expression domains. Birth Defects Res A Clin Mol Teratol. 67:59-67. Abstract

Laws SC, Ferrell JM, Stoker TE, Cooper RL. 2003. Pubertal development in female Wistar rats following exposure to propazine and atrazine biotransformation by-products, diamino-s-chlorotriazine and hydroxyatrazine. Toxicol Sci. 76:190-200. Abstract

Goldman JM, Murr AS. 2002. Alterations in ovarian follicular progesterone secretion by elevated exposures to the drinking water disinfection by-product dibromoacetic acid: examination of the potential site(s) of impact along the steroidogenic pathway. Toxicology. 171:83-93. Abstract

Stoker TE, Guidici DL, Laws SC, Cooper RL. 2002. The effects of atrazine metabolites on puberty and thyroid function in the male Wistar rat. Toxicol Sci. 6:198-206. Abstract

Environmental Carcinogenesis Division | Experimental Toxicology Division | Human Studies Division 
Neurotoxicology Division | Reproductive Toxicology Division

Local Navigation

Jump to main content.