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HORMONAL CONTROL OF OVARIAN FUNCTION FOLLOWING CHLOROTRIAZINE EXPOSURE: EFFECT ON REPRODUCTIVE FUNCTION AND MAMMARY GLAND TUMOR DEVELOPMENT
Citation:
Cooper, R L., S C. Laws, M G. Narotsky, J M. Goldman, AND T E. Stoker. HORMONAL CONTROL OF OVARIAN FUNCTION FOLLOWING CHLOROTRIAZINE EXPOSURE: EFFECT ON REPRODUCTIVE FUNCTION AND MAMMARY GLAND TUMOR DEVELOPMENT. Chapter 6, P.Hoyer (ed.), Ovarian Toxicology. CRC Press LLC, Boca Raton, FL, (2004).
Description:
Hormonal Control of Ovarian Function Following Chlorotriazine Exposure: Effect on Reproductive Function and Mammary Gland Tumor Development.
Ralph L. Cooper, Susan C. Laws, Michael G. Narotsky, Jerome M. Goldman, and Tammy E. Stoker
Abstract
The studies reviewed in this manuscript demonstrate that atrazine, the related chlorotriazine herbicides, and the chloroinated metabolites of these compounds disrupt the neuroendocrine control of ovarian function. The primary site of action of atrazine has been shown to be at the level of the hypothalamus. Prolonged atrazine exposure in the female rat appears to accelerate aging within the brain-pituitary-ovarian axis. This premature reproductive senescence (i.e., constant estrus) establishes the hormonal milieu conducive to the development of mammary gland tumors. As the causative factors associated with reproductive aging in the rat (impaired hypothalamic function) and human (depletion of primary follicles) are dramatically different, the possibility that a similar process may occur in women is remote. However, because the hypothalamic regulation of LH and prolactin secretion in the rat and human are similar, it is likely that the chlorotriazine herbicides could influence the secretion of these important pituitary hormones in humans. Importantly, the likelihood that the human would be exposed to these herbicides at the concentrations used in the rodent studies reviewed in this chapter appears remote (US EPA 2002). However, there are numerous chlorotriazine herbicides in use and these compounds produce metabolites that are similar to those of atrazine. Atrazine, other chlorotriazine herbicides, as well as their metabolites, are persistent in the groundwater (US EPA, 2002). Thus, the likelihood that humans may be exposed to these compounds in cumulative or combined manner, at concentrations that exceed the exceed the MCL (maximum concentration levels) for atrazine alone, must be considered.