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UNDERSTANDING THE EFFECTS OF ATRAZINE ON STEROIDOGENESIS IN THE HUMAN H295R AND RAT GRANULOSA CELLS
Citation:
TINFO, N. S., M. G. HOTCHKISS, S. C. LAWS, AND A. R. BUCKALEW. UNDERSTANDING THE EFFECTS OF ATRAZINE ON STEROIDOGENESIS IN THE HUMAN H295R AND RAT GRANULOSA CELLS. Presented at Society for the Study of Reproduction, Pittsburgh, PA, July 18 - 22, 2009.
Impact/Purpose:
Poster/Platform persentation for Annual Meeting of Society for the Study of Reproduction
Description:
The effects of environmental chemicals on the catalytic activity of steroidogenic enzymes, including aromatase, have been well documented. However, specific effects of environmental chemicals on steroidogenesis and the physiological impact on local and systemic concentrations of steroids have not yet been clearly demonstrated in laboratory animals. Recent in vitro studies have shown that atrazine (ATR), a chlorotriazine herbicide, induces aromatase gene expression in several human cell lines and may be associated with a stimulatory effect on NR5A receptors (SF-1, LRH-1) and second messenger signaling. Thus, these studies support the hypothesis of a specific cellular target through which ATR and potentially other environmental chemicals may alter aromatase expression, as well as other enzymes within the steroidogenic pathway. Using in vitro methods, we have evaluated the effects of ATR and metabolites on steroidogenesis in a human adrenal cell line (H295R) and primary rat granulosa cell cultures. ATR (10 and 30 uM) caused a significant increase in progesterone (P4), estrone and estradiol (E) in H295R cultures. To further investigate the effects of ATR on steroidogenesis, we evaluated the effects of ATR on E, and P4 production from rat granulosa cell cultures using different concentrations and exposure times. ATR and its metabolite DACT did not significantly alter E production at 24 hours in culture. Interestingly, aromatase activity was significantly increased following exposure to ATR (30 uM), with a corresponding increase in E within one hour of culture, indicating the importance of time in assessing the affects of ATR on steroidogenesis. However, DACT was not able to increase aromatase activity over control, and no increase in E was observed in the critical one hour period observed for ATR. As with the H295R studies, we observed a consistent increase in P4 following 24 hour exposure to ATR (10 and 30 uM). Furthermore, DACT was also able to significantly increase P4. Additional studies are ongoing to determine the cellular mechanisms through which ATR and its metabolites induce P4 synthesis in these culture systems. Thus, these studies support the hypothesis that ATR may have multiple effects on the steroidogenic pathway. This abstract does not necessarily reflect U.S.EPA policy.