FP38-3 The Herbicide, Atrazine, Mimics Restraint Stress in HPA Activation and Adrenal Morphological Changes

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP38-Physiological Impacts of Endocrine Disrupting Chemicals
Basic/Translational
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:55 AM
Room 256 (Moscone Center)

Poster Board MON-340
Arthur D Zimmerman*, Robert J Kemppainen and Chad D Foradori
Auburn University, College of Veterinary Medicine, Auburn, AL
Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine; ATR) is one of the most commonly used herbicides worldwide, with over 80 million pounds applied each year in the U.S. alone. It is used to stop both pre- and post-emergence broadleaf and grassy weeds, and has been applied on over 50 different crops including corn, sorghum and sugarcane. ATR’s effects on the hypothalamic-pituitary-gonadal (HPG) axis have been widely studied. ATR has been shown to inhibit both pulsatile luteinizing hormone (LH) release as well as the preovulatory LH surge. Recent evidence suggests that some of these effects are mediated by ATR’s effects on the hypothalamic-pituitary-adrenal (HPA) axis. ATR treatment leads to an increase in adrenocorticotropic hormone (ACTH) and, subsequently, corticosterone (CORT), which is a known inhibitor of the HPG axis. Indeed, we have shown that adrenalectomy will abolish ATR’s inhibition of LH pulsatile release. To determine how ATR activates the HPA axis and to measure effects of repeated ATR exposure on the adrenal gland, adult ovariectomized Sprague Dawley rats were gavaged daily with vehicle, 100 mg/kg of ATR or restrained for 30 min for 4 or 14 consecutive days. One hour after the final treatment, trunk blood was taken along with adrenal glands. The right adrenal was fixed in 10% buffered formalin for histology and the left was fast frozen for RNA quantification.  After 14 days, there was a reduction in ATR induced aldosterone and CORT release. In addition, ATR treatment led to a reduction in zona glomerulosa thickness and aldosterone synthase immunoreactivity with no change to zona fasciculata or 11β-hydroxylase. In each case, there were no differences found between ATR treated animals and those treated with repeated restraint stress. However, neurons in the paraventricular nuclei in the brains of ATR treated animals were not immunoreactive for the cell activation marker, FOS, suggesting ATR does not activate the primary neural integration site in the stress response. In addition, ATR did not elicit ACTH release from immortalized corticotrophs (AtT- 20) or potentiate the cAMP induced release. In conclusion, ATR’s induced adrenal activation and morphological changes mimic those of repeated stress, however, ATR appears to activate the HPA axis using a novel and yet undetermined mechanism.

Disclosure: CDF: Principal Investigator, Syngenta Crop Protection, Inc.. Nothing to Disclose: ADZ, RJK

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Animal Health and Disease, IGP, Auburn University