ToxSci Advance Access originally published online on March 31, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Toxicological Sciences 79, 278-286 (2004)
Toxicological Sciences vol. 79 no. 2 © Society of Toxicology; all rights reserved.
Evidence That Atrazine and Diaminochlorotriazine Inhibit the Estrogen/Progesterone Induced Surge of Luteinizing Hormone in Female Sprague-Dawley Rats Without Changing Estrogen Receptor Action
* Department of Environmental and Radiological Health Sciences, and Department of Biomedical Sciences, Colorado State University,Fort Collins, Colorado 80523
Received December 31, 2003; accepted March 1, 2004
High oral doses of atrazine (ATRA) disrupt normal neuroendocrine function, resulting in suppression of the luteinizing hormone (LH) surge in adult, ovariectomized (OVX) estrogen-primed female rats. While the mechanism by which ATRA inhibits LH secretion is not known, current data indicate that ATRA does have anti-estrogenic properties in vitro and in vivo. In the body, ATRA is rapidly converted to diaminochlorotriazine (DACT). The present study was conducted to investigate the effects of ATRA and DACT on the estradiol benzoate (EB)/progesterone (P) induced LH surge and to determine if such changes correlate with impaired estrogen receptor (ER) function. ATRA, administered by gavage for five consecutive days to adult OVX, female Sprague-Dawley rats, caused a dose-dependent suppression of the EB/P induced LH surge. Although to a lesser degree than ATRA, DACT significantly suppressed total plasma LH and peak LH surge levels in EB/P primed animals by 60 and 58%, respectively. DACT treatment also decreased release of LH from the pituitary in response to exogenous gonadotropin releasing hormone (GnRH) by 47% compared to control. Total plasma LH secretion was reduced by 37% compared to control, suggesting that in addition to potential hypothalamic dysfunction, pituitary function is altered. To further investigate the mechanism by which hypothalamic function might be altered, potential anti-estrogenicity of ATRA and DACT were assessed by evaluating ER function treated rats. Using an in vitro receptor binding assay, ATRA, but not DACT, inhibited binding of [3H]-estradiol to ER. In contrast, ATRA, administered to female rats under dosing conditions which suppressed the LH surge, neither changed the levels of unoccupied ER nor altered the estrogen induced up-regulation of progesterone receptor mRNA. Collectively, these results indicate that although ATRA is capable of binding ER in vitro, the suppression of LH after treatment with high doses of ATRA is not due to alterations of hypothalamic ER function.
Key Words: atrazine; chlorotriazines; estrogen receptor; DACT; brain; hypothalamus.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. C. Laws, M. Hotchkiss, J. Ferrell, S. Jayaraman, L. Mills, W. Modic, N. Tinfo, M. Fraites, T. Stoker, and R. Cooper Chlorotriazine Herbicides and Metabolites Activate an ACTH-dependent Release of Corticosterone in Male Wistar Rats Toxicol. Sci., November 1, 2009; 112(1): 78 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. P. Fraites, R. L. Cooper, A. Buckalew, S. Jayaraman, L. Mills, and S. C. Laws Characterization of the Hypothalamic-Pituitary-Adrenal Axis Response to Atrazine and Metabolites in the Female Rat Toxicol. Sci., November 1, 2009; 112(1): 88 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Foradori, L. R. Hinds, W. H. Hanneman, M. E. Legare, C. M. Clay, and R. J. Handa Atrazine Inhibits Pulsatile Luteinizing Hormone Release Without Altering Pituitary Sensitivity to a Gonadotropin-Releasing Hormone Receptor Agonist in Female Wistar Rats Biol Reprod, July 1, 2009; 81(1): 40 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Caserta, L. Maranghi, A. Mantovani, R. Marci, F. Maranghi, and M. Moscarini Impact of endocrine disruptor chemicals in gynaecology Hum. Reprod. Update, January 1, 2008; 14(1): 59 - 72. [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]
|
|
|
|
|
|
K. W. Wilhelms, S. A. Cutler, J. A. Proudman, L. L. Anderson, and C. G. Scanes Atrazine and the Hypothalamo-Pituitary-Gonadal Axis in Sexually Maturing Precocial Birds: Studies in Male Japanese Quail Toxicol. Sci., July 1, 2005; 86(1): 152 - 160. [Abstract] [Full Text] [PDF]
|
|