Atrazine‐induced changes in aromatase activity in estrogen sensitive target tissues

Abstract

Atrazine (ATR) is a pesticide used widely throughout North America. Although not directly estrogenic, ATR treatment has been shown to increase aromatase activity in tumor cell lines. Thus, it is suggested that ATR can increase local tissue estrogen levels in estrogen sensitive target tissues through increased aromatase activity. Therefore the effect of ATR on aromatase activity was measured in human granulosa-lutein cell cultures, cells that abundantly express aromatase, and endometrial stromal cell (ESC) cultures, cells that do not express aromatase. Aromatase activity was quantified by the tritiated water method and the specificity of the assay was confirmed by co-incubation with 4-hydroxyandrostenedione, an irreversible inhibitor of the catalytic activity of aromatase. Aromatase activity in ATR treated (1-10 microm) granulosa-lutein cells was increased more than 2-fold compared with control cultures. There were no treatment related changes in cellular protein and thus it is suggested that the ATR-induced change in aromatase activity was not due to an increase in cell number. ATR-treatment had no effect on ESC aromatase activity at any concentration tested. Similarly, there was no effect of ATR treatment on human recombinant aromatase activity in our cell-free test system. Therefore it is concluded that microm concentrations of ATR can increase aromatase activity of human granulosa cells but not ESC and this effect is not elicited at the enzyme level.

Quantification of steroids and endocrine disrupting chemicals in rat ovaries by LC-MS/MS for reproductive toxicology assessment

“…6). ATZ, MXC, and BPA are classified as estrogenic, according to in vitro studies [4,5,7]. However, the effects on hormonal balance in our study are more or less important.…”

“…Of high concern is the impact of EDCs on the reproductive system [3]. Among them, atrazine (ATZ), bisphenol A (BPA), methoxychlor (MXC), and vinclozolin (VCZ) have long been studied and have been described as estrogeno-mimetic (ATZ, BPA, and MXC) or anti-androgenic (VCZ) in vitro [4][5][6][7]. Despite the high importance of the androgen-to-estrogen balance in evaluating reproductive effects [8], the great majority of in vivo studies have dealt with the determination of estrogens in females and androgens in males [9].…”

Gene expression profiles in testis of developing male Xenopus laevis damaged by chronic exposure of atrazine

“…AZ has been reported to cause endocrine disruption in mammals, birds, reptiles, fish and amphibians by affecting normal reproductive function and development in these organisms (Holloway et al, 2008;Gunderson et al, 2011;Kloas et al, 2009;de la Casa-Resino, 2012;Rohr and McCoy, 2010).…”

Oxidation of retinoic acids in hepatic microsomes of wild bullfrogs Lithobates catesbeianus environmentally-exposed to a gradient of agricultural contamination

“…Most of these contaminants have been found to influence the development and the growth of aquatic wildlife as well as the activity of several CYP450s. For years the effects of atrazine on frogs have focused on the feminization of male frogs via the modulation of P450aromatase pathway (Halloway et al 2008;Hayes et al 2010). In X. laevis tadpoles, atrazine decreased intestine XCYP26 activity and increased RA concentration leading to a higher susceptibility to apoptosis (Lenkowski and McLaughlin 2010).…”