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Atrazine binds to the growth hormone-releasing hormone receptor and affects growth hormone gene expression.

Fakhouri WD, Nuñez JL, Trail F - Environ. Health Perspect. (2010)

Bottom Line: The treatment of rat pituitary cells with ATR, at environmentally relevant concentrations (1 ppb and 1 ppm), resulted in a reduction of GH expression.This effect appeared to result from the inhibition of GH gene transcription due to ATR binding to the GHRHR of the pituitary cells.These findings may lead to a better understanding of the hazards of environmental ATR contamination and inform efforts to develop guidelines for establishing safe levels in water systems.

View Article: PubMed Central - PubMed

Affiliation: Department of Plant Biology, Michigan State University, East Lansing, Michigan 48824, USA.

ABSTRACT

Background: Atrazine (ATR), a commonly used herbicide in the United States, is widely distributed in water and soil because of its mobility through ecosystems and its persistence in the environment. ATR has been associated with defects in sexual development in animals, but studies on mammalian systems have failed to clearly identify a cellular target.

Objectives: Our goal in this study was to identify a ligand-binding receptor for ATR in pituitary cells that may explain the mechanism of action at the gene expression level.

Methods: We used pituitary cells from postnatal day 7 male rats and pituitary cell lines to study the effect of ATR on gene expression of growth hormone (GH), luteinizing hormone (LH), and prolactin (PRL) at RNA and protein levels. 14C-ATR was used to determine its specific binding to the growth hormone-releasing hormone receptor (GHRHR). The effect of ATR on structural proteins was visualized using immunofluorescent in situ staining.

Results: The treatment of rat pituitary cells with ATR, at environmentally relevant concentrations (1 ppb and 1 ppm), resulted in a reduction of GH expression. This effect appeared to result from the inhibition of GH gene transcription due to ATR binding to the GHRHR of the pituitary cells.

Conclusions: Identification of GHRHR as the target of ATR is consistent with the myriad effects previously reported for ATR in mammalian systems. These findings may lead to a better understanding of the hazards of environmental ATR contamination and inform efforts to develop guidelines for establishing safe levels in water systems.

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Expression (mean ± SE) of GH, LH, and PRL genes in rat pituitary cells treated with DMSO (control) or with 1.0 ppb or 1.0 ppm ATR. Cells were harvested 72 hr after treatment, and gene expression was measured by real-time qPCR; data were normalized to levels of histone H3 mRNA.
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f1-ehp-118-1400: Expression (mean ± SE) of GH, LH, and PRL genes in rat pituitary cells treated with DMSO (control) or with 1.0 ppb or 1.0 ppm ATR. Cells were harvested 72 hr after treatment, and gene expression was measured by real-time qPCR; data were normalized to levels of histone H3 mRNA.

Mentions: Previous work has demonstrated that neonatal ATR exposure affects the sexual development of frogs, turning them into hermaphrodites (having sexual characteristics of both males and females) (Hayes et al. 2002b; Kniewald et al. 2000). ATR may likewise affect the neuroendocrine axis in mammals. The critical period for sexual differentiation of the rodent brain occurs between embryonic day 18 and PND10 (Arnold and Breedlove 1985). Given that ATR exposure may have the potential to affect sexual differentiation of the rodent brain and that preliminary investigations suggest that the survival of pituitary cells in culture is maximal at the end of the first postnatal week (Nuñez JL, personal communication), we cultured pituitary cells on PND7. Exposure of pituitary cells to 1.0 ppm ATR resulted in a remarkable reduction in the mRNA levels of genes encoding GH and LH (Figure 1). However, levels of PRL mRNA increased in the treated cells compared with controls.


Atrazine binds to the growth hormone-releasing hormone receptor and affects growth hormone gene expression.

Fakhouri WD, Nuñez JL, Trail F - Environ. Health Perspect. (2010)

Expression (mean ± SE) of GH, LH, and PRL genes in rat pituitary cells treated with DMSO (control) or with 1.0 ppb or 1.0 ppm ATR. Cells were harvested 72 hr after treatment, and gene expression was measured by real-time qPCR; data were normalized to levels of histone H3 mRNA.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2957919&req=5

f1-ehp-118-1400: Expression (mean ± SE) of GH, LH, and PRL genes in rat pituitary cells treated with DMSO (control) or with 1.0 ppb or 1.0 ppm ATR. Cells were harvested 72 hr after treatment, and gene expression was measured by real-time qPCR; data were normalized to levels of histone H3 mRNA.
Mentions: Previous work has demonstrated that neonatal ATR exposure affects the sexual development of frogs, turning them into hermaphrodites (having sexual characteristics of both males and females) (Hayes et al. 2002b; Kniewald et al. 2000). ATR may likewise affect the neuroendocrine axis in mammals. The critical period for sexual differentiation of the rodent brain occurs between embryonic day 18 and PND10 (Arnold and Breedlove 1985). Given that ATR exposure may have the potential to affect sexual differentiation of the rodent brain and that preliminary investigations suggest that the survival of pituitary cells in culture is maximal at the end of the first postnatal week (Nuñez JL, personal communication), we cultured pituitary cells on PND7. Exposure of pituitary cells to 1.0 ppm ATR resulted in a remarkable reduction in the mRNA levels of genes encoding GH and LH (Figure 1). However, levels of PRL mRNA increased in the treated cells compared with controls.

Bottom Line: The treatment of rat pituitary cells with ATR, at environmentally relevant concentrations (1 ppb and 1 ppm), resulted in a reduction of GH expression.This effect appeared to result from the inhibition of GH gene transcription due to ATR binding to the GHRHR of the pituitary cells.These findings may lead to a better understanding of the hazards of environmental ATR contamination and inform efforts to develop guidelines for establishing safe levels in water systems.

View Article: PubMed Central - PubMed

Affiliation: Department of Plant Biology, Michigan State University, East Lansing, Michigan 48824, USA.

ABSTRACT

Background: Atrazine (ATR), a commonly used herbicide in the United States, is widely distributed in water and soil because of its mobility through ecosystems and its persistence in the environment. ATR has been associated with defects in sexual development in animals, but studies on mammalian systems have failed to clearly identify a cellular target.

Objectives: Our goal in this study was to identify a ligand-binding receptor for ATR in pituitary cells that may explain the mechanism of action at the gene expression level.

Methods: We used pituitary cells from postnatal day 7 male rats and pituitary cell lines to study the effect of ATR on gene expression of growth hormone (GH), luteinizing hormone (LH), and prolactin (PRL) at RNA and protein levels. 14C-ATR was used to determine its specific binding to the growth hormone-releasing hormone receptor (GHRHR). The effect of ATR on structural proteins was visualized using immunofluorescent in situ staining.

Results: The treatment of rat pituitary cells with ATR, at environmentally relevant concentrations (1 ppb and 1 ppm), resulted in a reduction of GH expression. This effect appeared to result from the inhibition of GH gene transcription due to ATR binding to the GHRHR of the pituitary cells.

Conclusions: Identification of GHRHR as the target of ATR is consistent with the myriad effects previously reported for ATR in mammalian systems. These findings may lead to a better understanding of the hazards of environmental ATR contamination and inform efforts to develop guidelines for establishing safe levels in water systems.

Show MeSH