Toxicological Sciences 53, 297-307 (2000)
Copyright © 2000 by the Society of Toxicology
Atrazine Disrupts the Hypothalamic Control of Pituitary-Ovarian Function
* Endocrinology Branch, Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711; and
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina 27710
The chloro-S-triazine herbicides (i.e., atrazine, simazine, cyanazine) constitute the largest group of herbicides sold in the United States. Despite their extensive usage, relatively little is known about the possible human-health effects and mechanism(s) of action of these compounds. Previous studies in our laboratory have shown that the chlorotriazines disrupt the hormonal control of ovarian cycles. Results from these studies led us to hypothesize that these herbicides disrupt endocrine function primarily through their action on the central nervous system. To evaluate this hypothesis, we examined the estrogen-induced surges of luteinizing hormone (LH) and prolactin in ovariectomized Sprague-Dawley (SD) and Long-Evans hooded (LE) rats treated with atrazine (50–300 mg/kg/day, by gavage) for 1, 3, or 21 days. One dose of atrazine (300 mg/kg) suppressed the LH and prolactin surge in ovariectomized LE, but not SD female rats. Atrazine (300 mg/kg) administered to intact LE females on the day of vaginal proestrus was without effect on ovulation but did induce a pseudopregnancy in 7 of 9 females. Three daily doses of atrazine suppressed the estrogen-induced LH and prolactin surges in ovariectomized LE females in a dose-dependent manner, but this same treatment was without effect on serum LH and prolactin in SD females. The estrogen-induced surges of both pituitary hormones were suppressed by atrazine (75–300 mg/kg/day) in a dose-dependent manner in females of both strains evaluated after 21 days of treatment. Three experiments were then performed to determine whether the brain, pituitary, or both organs were the target sites for the chlorotriazines. These included examination of the ability of (1) the pituitary lactotrophs to secrete prolactin, using hypophyosectomized females bearing pituitary autotransplants (ectopic pituitaries); (2) the synthetic gonadotropin-releasing hormone (GnRH) to induce LH secretion in females treated with high concentrations of atrazine for 3 days; and (3) atrazine (administered in vivo or in vitro) to suppress LH and prolactin secretion from pituitaries, using a flow-through perifusion procedure. In conclusion, the results of these studies demonstrate that atrazine alters LH and prolactin serum levels in the LE and SD female rats by altering the hypothalamic control of these hormones. In this regard, the LE female appeared to be more sensitive to the hormone suppressive effects of atrazine, as indicated by the decreases observed on treatment-day 3. These experiments support the hypothesis that the effect of atrazine on LH and prolactin secretion is mediated via a hypothalamic site of action.
Key Words: atrazine; prolactin; luteinizing hormone; hypothalamus; reproduction.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. G. Rosenberg, H. Chen, J. Folmer, J. Liu, V. Papadopoulos, and B. R. Zirkin Gestational Exposure to Atrazine: Effects on the Postnatal Development of Male Offspring J Androl, May 1, 2008; 29(3): 304 - 311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. G. Coburn, M. C. Curras-Collazo, and P. R. S. Kodavanti Polybrominated Diphenyl Ethers and ortho-Substituted Polychlorinated Biphenyls as Neuroendocrine Disruptors of Vasopressin Release: Effects during Physiological Activation In Vitro and Structure-Activity Relationships Toxicol. Sci., July 1, 2007; 98(1): 178 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Sanderson The Steroid Hormone Biosynthesis Pathway as a Target for Endocrine-Disrupting Chemicals Toxicol. Sci., November 1, 2006; 94(1): 3 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. V. Rider and G. A. LeBlanc Atrazine Stimulates Hemoglobin Accumulation in Daphnia magna: Is it Hormonal or Hypoxic? Toxicol. Sci., October 1, 2006; 93(2): 443 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Farr, J. Cai, D. A. Savitz, D. P. Sandler, J. A. Hoppin, and G. S. Cooper Pesticide Exposure and Timing of Menopause: The Agricultural Health Study Am. J. Epidemiol., April 15, 2006; 163(8): 731 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Giusi, R. M. Facciolo, M. Canonaco, E. Alleva, V. Belloni, F. Dessi'-Fulgheri, and D. Santucci The Endocrine Disruptor Atrazine Accounts for a Dimorphic Somatostatinergic Neuronal Expression Pattern in Mice Toxicol. Sci., January 1, 2006; 89(1): 257 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Filipov, L. M. Pinchuk, B. L. Boyd, and P. L. Crittenden Immunotoxic Effects of Short-term Atrazine Exposure in Young Male C57BL/6 Mice Toxicol. Sci., August 1, 2005; 86(2): 324 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hecker, J.-W. Park, M. B. Murphy, P. D. Jones, K. R. Solomon, G. Van Der Kraak, J. A. Carr, E. E. Smith, L. du Preez, R. J. Kendall, et al. Effects of Atrazine on CYP19 Gene Expression and Aromatase Activity in Testes and on Plasma Sex Steroid Concentrations of Male African Clawed Frogs (Xenopus laevis) Toxicol. Sci., August 1, 2005; 86(2): 273 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Stoker, S. D. Perreault, K. Bremser, R. S. Marshall, A. Murr, and R. L. Cooper Acute Exposure to Molinate Alters Neuroendocrine Control of Ovulation in the Rat Toxicol. Sci., March 1, 2005; 84(1): 38 - 48. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Farr, G. S. Cooper, J. Cai, D. A. Savitz, and D. P. Sandler Pesticide Use and Menstrual Cycle Characteristics among Premenopausal Women in the Agricultural Health Study Am. J. Epidemiol., December 15, 2004; 160(12): 1194 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. S. McMullin, M. E. Andersen, A. Nagahara, T. D. Lund, T. Pak, R. J. Handa, and W. H. Hanneman Evidence That Atrazine and Diaminochlorotriazine Inhibit the Estrogen/Progesterone Induced Surge of Luteinizing Hormone in Female Sprague-Dawley Rats Without Changing Estrogen Receptor Action Toxicol. Sci., June 1, 2004; 79(2): 278 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Rooney, R. A. Matulka, and R. W. Luebke Developmental Atrazine Exposure Suppresses Immune Function in Male, but not Female Sprague-Dawley Rats Toxicol. Sci., December 1, 2003; 76(2): 366 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Laws, J. M. Ferrell, T. E. Stoker, and R. L. Cooper Pubertal Development in Female Wistar Rats following Exposure to Propazine and Atrazine Biotransformation By-Products, Diamino-S-Chlorotriazine and Hydroxyatrazine Toxicol. Sci., November 1, 2003; 76(1): 190 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Stoker, S. C. Jeffay, R. M. Zucker, R. L. Cooper, and S. D. Perreault Abnormal Fertilization Is Responsible for Reduced Fecundity Following Thiram-Induced Ovulatory Delay in the Rat Biol Reprod, June 1, 2003; 68(6): 2142 - 2149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wright, A.C.O. Evans, N.P. Evans, P. Duffy, J. Fox, M.P. Boland, J.F. Roche, and T. Sweeney Effect of Maternal Exposure to the Environmental Estrogen, Octylphenol, During Fetal and/or Postnatal Life on Onset of Puberty, Endocrine Status, and Ovarian Follicular Dynamics in Ewe Lambs Biol Reprod, December 1, 2002; 67(6): 1734 - 1740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Stoker, D. L. Guidici, S. C. Laws, and R. L. Cooper The Effects of Atrazine Metabolites on Puberty and Thyroid Function in the Male Wistar Rat Toxicol. Sci., June 1, 2002; 67(2): 198 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Fenton, J. T. Hamm, L. S. Birnbaum, and G. L. Youngblood Persistent Abnormalities in the Rat Mammary Gland following Gestational and Lactational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Toxicol. Sci., May 1, 2002; 67(1): 63 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. B. Hayes, A. Collins, M. Lee, M. Mendoza, N. Noriega, A. A. Stuart, and A. Vonk Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses PNAS, April 16, 2002; 99(8): 5476 - 5480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Das, W. K. McElroy, and R. L. Cooper Alteration of Catecholamines in Pheochromocytoma (PC12) Cells in Vitro by the Metabolites of Chlorotriazine Herbicide Toxicol. Sci., January 1, 2001; 59(1): 127 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Laws, J. M. Ferrell, T. E. Stoker, J. Schmid, and R. L. Cooper The Effects of Atrazine on Female Wistar Rats: An Evaluation of the Protocol for Assessing Pubertal Development and Thyroid Function Toxicol. Sci., December 1, 2000; 58(2): 366 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Stoker, S. C. Laws, D. L. Guidici, and R. L. Cooper The Effect of Atrazine on Puberty in Male Wistar Rats: An Evaluation in the Protocol for the Assessment of Pubertal Development and Thyroid Function Toxicol. Sci., November 1, 2000; 58(1): 50 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Cummings, B. E. Rhodes, and R. L. Cooper Effect of Atrazine on Implantation and Early Pregnancy in 4 Strains of Rats Toxicol. Sci., November 1, 2000; 58(1): 135 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Das, W. K. McElroy, and R. L. Cooper Differential Modulation of Catecholamines by Chlorotriazine Herbicides in Pheochromocytoma (PC12) Cells in Vitro Toxicol. Sci., August 1, 2000; 56(2): 324 - 331. [Abstract] [Full Text] [PDF]
|
|