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BPA Directly Decreases GnRH Neuronal Activity via Noncanonical Pathway.

ABSTRACT: Peripheral feedback of gonadal estrogen to the hypothalamus is critical for reproduction. Bisphenol A (BPA), an environmental pollutant with estrogenic actions, can disrupt this feedback and lead to infertility in both humans and animals. GnRH neurons are essential for reproduction, serving as an important link between brain, pituitary, and gonads. Because GnRH neurons express several receptors that bind estrogen, they are potential targets for endocrine disruptors. However, to date, direct effects of BPA on GnRH neurons have not been shown. This study investigated the effects of BPA on GnRH neuronal activity using an explant model in which large numbers of primary GnRH neurons are maintained and express many of the receptors found in vivo. Because oscillations in intracellular calcium have been shown to correlate with electrical activity in GnRH neurons, calcium imaging was used to assay the effects of BPA. Exposure to 50?M BPA significantly decreased GnRH calcium activity. Blockage of ?-aminobutyric acid ergic and glutamatergic input did not abrogate the inhibitory BPA effect, suggesting direct regulation of GnRH neurons by BPA. In addition to estrogen receptor-?, single-cell RT-PCR analysis confirmed that GnRH neurons express G protein-coupled receptor 30 (G protein-coupled estrogen receptor 1) and estrogen-related receptor-?, all potential targets for BPA. Perturbation studies of the signaling pathway revealed that the BPA-mediated inhibition of GnRH neuronal activity occurred independent of estrogen receptors, GPER, or estrogen-related receptor-?, via a noncanonical pathway. These results provide the first evidence of a direct effect of BPA on GnRH neurons.

SUBMITTER: Klenke U

PROVIDER: S-EPMC4870872 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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BPA Directly Decreases GnRH Neuronal Activity via Noncanonical Pathway.

Klenke Ulrike U Constantin Stephanie S Wray Susan S

Endocrinology 20160302 5

Peripheral feedback of gonadal estrogen to the hypothalamus is critical for reproduction. Bisphenol A (BPA), an environmental pollutant with estrogenic actions, can disrupt this feedback and lead to infertility in both humans and animals. GnRH neurons are essential for reproduction, serving as an important link between brain, pituitary, and gonads. Because GnRH neurons express several receptors that bind estrogen, they are potential targets for endocrine disruptors. However, to date, direct effe ...[more]

PMID: 26934298

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BPA Directly Decreases GnRH Neuronal Activity via Noncanonical Pathway.

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BPA Directly Decreases GnRH Neuronal Activity via Noncanonical Pathway.

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