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Understanding the Effects of Atrazine on Steroidogenesis in rat granulosa and H295R adrenal cortical carcinoma cells
Citation:
LAWS, S. C., M. G. HOTCHKISS, A. R. BUCKALEW, R. L. COOPER, N. Tinfo, AND L. Zorrilla. Understanding the Effects of Atrazine on Steroidogenesis in rat granulosa and H295R adrenal cortical carcinoma cells. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 31(2):184-93, (2011).
Impact/Purpose:
The in vitro data reported in this manuscript demonstrates that atrazine stimulates aromataseactivity in human H295R cell cultures and in rat primary granulosa cell culture when testedunder a rigid exposure regimen. In addition, these data showed a robust effect on progesterone synthesis in both the H295R and granulosa cell cultures. These results support the studies by Suzawa et al. (PLoS ONE, 2008; 3(5): e2117) that showed an atrazine induced expression of multiple genes for steroidogenic enzymes in JEG-3 cells. Importantly, this study suggests that atrazine can directly target ovarian and adrenal cells during in vivo exposures,and that this may occur in addition to the ACTH-dependent increase in serum progesterone and corticosterone reported in Laws et al. (Toxicol. Sci., 2009; 112(1): 78-87). Taken together, these studies support the hypothesis that elevated serum estrogens observed in rats may be due to an increase in substrate of ovarian and/or adrenal origin. In addition, these studies demonstrate the challenges of study design for in vitro and in vivo studied of steroidogenesis, and identify issues that may confound data interpretation.
Description:
Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) was introduced in the 1950s as a broad spectrum herbicide, and remains one of the most widely used herbicides in the United States. Several studies have suggested that atrazine modifies steroidogenesis and may disrupt reproductive function and development in a variety of species. A primary concern has been whether atrazine increases the synthesis of estrogens, perhaps by enhancing aromatase gene expression and activity. In this study, the effect of atrazine was compared in cultures using primary granulosa cells and H295R adrenal cortical carcinoma cells. Atrazine (10 IJM), but not its metabolite, 2chloro- 4, 6-diamino-1 ,2,5-triazine (DACT), significantly increased estradiol production and aromatase activity in granulosa cell cultures only when measured during a 1-hour interval following 24 hours of exposure. In H295R cells, atrazine (10 IJM) increased estradiol and estrone production. Importantly, atrazine (10 IJM) increased progesterone production from both cell types suggesting a broader effect of atrazine on steroidogenesis.
