Herbicide atrazine activates SF-1 by direct affinity and concomitant co-activators recruitments to induce aromatase expression via promoter II

Fan, Wu; Yanase, Toshihiko; Morinaga, Hidetaka; Gondo, Shigeki; Okabe, Taijiro; Nomura, Masatoshi; Hayes, Tyrone B.; Takayanagi, Ryoichi; Nawata, Hajime

doi:10.1016/j.bbrc.2007.02.062

Cited by 66 publications

(38 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to its persistence, mobility, and widespread contamination of water, atrazine is also a concern because several studies have shown that atrazine is a potent endocrine disruptor active in the ppb (parts per billion) range in fish (4, 5), amphibians (6)(7)(8)(9)(10)(11)(12), reptiles, and human cell lines (5,(13)(14)(15), and at higher doses (ppm) in reptiles (16)(17)(18), birds (19), and laboratory rodents (20)(21)(22)(23)(24)(25)(26)(27)(28). Atrazine seems to be most potent in amphibians, where it is active at levels as low as 0.1 ppb (6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis)

Hayes

Khoury

Narayan

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

514

307

View full text Add to dashboard Cite

The herbicide atrazine is one of the most commonly applied pesticides in the world. As a result, atrazine is the most commonly detected pesticide contaminant of ground, surface, and drinking water. Atrazine is also a potent endocrine disruptor that is active at low, ecologically relevant concentrations. Previous studies showed that atrazine adversely affects amphibian larval development. The present study demonstrates the reproductive consequences of atrazine exposure in adult amphibians. Atrazineexposed males were both demasculinized (chemically castrated) and completely feminized as adults. Ten percent of the exposed genetic males developed into functional females that copulated with unexposed males and produced viable eggs. Atrazineexposed males suffered from depressed testosterone, decreased breeding gland size, demasculinized/feminized laryngeal development, suppressed mating behavior, reduced spermatogenesis, and decreased fertility. These data are consistent with effects of atrazine observed in other vertebrate classes. The present findings exemplify the role that atrazine and other endocrine-disrupting pesticides likely play in global amphibian declines.A trazine is one of the most widely used pesticides in the world. Approximately 80 million pounds are applied annually in the United States alone, and atrazine is the most common pesticide contaminant of ground and surface water (1). Atrazine can be transported more than 1,000 km from the point of application via rainfall and, as a result, contaminates otherwise pristine habitats, even in remote areas where it is not used (2, 3). In fact, more than a half million pounds of atrazine are precipitated in rainfall each year in the United States (2).In addition to its persistence, mobility, and widespread contamination of water, atrazine is also a concern because several studies have shown that atrazine is a potent endocrine disruptor active in the ppb (parts per billion) range in fish (4, 5), amphibians (6-12), reptiles, and human cell lines (5, 13-15), and at higher doses (ppm) in reptiles (16-18), birds (19), and laboratory rodents (20-28). Atrazine seems to be most potent in amphibians, where it is active at levels as low as 0.1 ppb (6-10). Although a few studies suggest that atrazine has no effect on amphibians under certain laboratory conditions (29,30), in other studies, atrazine reduces testicular volume; reduces germ cell and Sertoli cell numbers (11); induces hermaphroditism (6, 8, 10); reduces testosterone (10); and induces testicular oogenesis (7-9, 31). Furthermore, atrazine contamination is associated with demasculinization and feminization of amphibians in agricultural areas where atrazine is used (32) and directly correlated with atrazine contamination in the wild (7,9,33,34).Despite the wealth of data from larvae and newly metamorphosed amphibians, the ultimate impacts of atrazine's developmental effects on reproductive function and fitness at sexual maturity, which relate more closely to population level effects and amphibian declines, have b...

show abstract

mentioning

confidence: 99%

Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis)

Hayes

Khoury

Narayan

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

514

307

View full text Add to dashboard Cite

show abstract

“…Atrazine disrupts the hypothalamo-pituitary-gonadal (HPG) axis via multiple mechanisms. This EDC increases expression of the enzyme aromatase [14][15][16][17] which converts aromatisable androgens to estrogens. 18 Atrazine also decreases circulating HPG hormones including gonadotrophin releasing hormone (GnRH), luteinizing hormone (LH) [19][20][21] and the androgen dihydrotestosterone (DHT), 22 and alters DHT availability.…”

Section: Introductionmentioning

confidence: 99%

“…12,18,23 The rodent placenta is therefore unlikely to be a site of disruption by ATZ. Secondly, ATZ disrupts aromatase expression in tissues which express aromatase via the ArPII promoter in cells that also express steroidogenic factor 1 (SF-1) 14,15 but in female rat embryos SF-1 is not active in the differentiating ovary until just before birth. 24 Thus disruption to various reproductive indices in laboratory rodents occurs only at concentrations of ATZ (1000 ppb-100 ppm) which are far above those of ecological relevance.…”

Section: Introductionmentioning

confidence: 99%

Atrazine disrupts gonadal development in a live-bearing lizard

Parsley

Wapstra

Jones

2015

Endocrine Disruptors

View full text Add to dashboard Cite

Atrazine (ATZ) is an endocrine disruptor that increases aromatase activity. In viviparous (live-bearing) vertebrates, embryos may be exposed to endocrine disruptors via the placenta. Studies of the effects of ATZ in viviparous amniotes have focused on rodents, which are relatively insensitive to ATZ: studies on other viviparous amniotes are therefore required. We aimed to determine the effects of gestational exposure to a single dose of ATZ at 10 ppb on gonadal development in a viviparous skink, Niveoscincus metallicus. Pregnant skinks were exposed to ATZ, the synthetic estrogen diethylstilbestrol (DES) (positive control), vehicle solvent or no treatment. Gonads were examined histologically at birth. Females born to ATZ and DES exposed mothers were more likely to exhibit ovaries with abnormal oocytes than were females whose mothers received vehicle solvent or no treatment. Males born to ATZ and DES exposed mothers were equally more likely to exhibit testes devoid of germ cells with reduced organization of seminiferous tubules (ST) compared to males born to mothers receiving vehicle solvent or no treatment. However, ATZ treatment significantly increased the number of male neonates born with testicular lesions compared to males born to mothers in any other group. We conclude that atrazine disrupts gonadal differentiation in the viviparous lizard, N. metallicus. The similar effects of DES and ATZ suggest that the developmental effects of ATZ in N. metallicus reflect increased estrogen signaling. Atrazine should be used with caution as exposure of wildlife to this EDC is likely to have adverse effects on reproductive health.

show abstract

“…2 In fact, atrazine is an endocrine disruptor and corelates with breast and reproductive disorders in mammalians. 3 Atrazine at present is widely used in USA and, although it has been withdrawn from the market in several European countries, analogous molecules (as terbuthylazine differing only by side chain methyl groups) are currently used. 4 Furthermore, although banned in Europe in 1980, atrazine is still present as a contaminant in several surface and ground water sites at concentrations higher than imposed by EU directives.…”

Section: Introductionmentioning

confidence: 99%

Structure‐based design of novel Chlamydomonas reinhardtii D1‐D2 photosynthetic proteins for herbicide monitoring

et al. 2009

View full text Add to dashboard Cite

The D1-D2 heterodimer in the reaction center core of phototrophs binds the redox plastoquinone cofactors, Q A and Q B , the terminal acceptors of the photosynthetic electron transfer chain in the photosystem II (PSII). This complex is the target of the herbicide atrazine, an environmental pollutant competitive inhibitor of Q B binding, and consequently it represents an excellent biomediator to develop biosensors for pollutant monitoring in ecosystems. In this context, we have undertaken a study of the Chlamydomonas reinhardtii D1-D2 proteins aimed at designing site directed mutants with increased affinity for atrazine. The three-dimensional structure of the D1 and D2 proteins from C. reinhardtii has been homology modeled using the crystal structure of the highly homologous Thermosynechococcus elongatus proteins as templates. Mutants of D1 and D2 were then generated in silico and the atrazine binding affinity of the mutant proteins has been calculated to predict mutations able to increase PSII affinity for atrazine. The computational approach has been validated through comparison with available experimental data and production and characterization of one of the predicted mutants. The latter analyses indicated an increase of one order of magnitude of the mutant sensitivity and affinity for atrazine as compared to the control strain. Finally, D1-D2 heterodimer mutants were designed and selected which, according to our model, increase atrazine binding affinity by up to 20 kcal/mol, representing useful starting points for the development of high affinity biosensors for atrazine.

show abstract

Herbicide atrazine activates SF-1 by direct affinity and concomitant co-activators recruitments to induce aromatase expression via promoter II

Cited by 66 publications

References 22 publications

Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis)

Atrazine induces complete feminization and chemical castration in male African clawed frogs (Xenopus laevis)

Atrazine disrupts gonadal development in a live-bearing lizard

Structure‐based design of novel Chlamydomonas reinhardtii D1‐D2 photosynthetic proteins for herbicide monitoring

Contact Info

Product

Resources

About