Microcystin-LR causes sexual hormone disturbance in male rat by targeting gonadotropin-releasing hormone neurons

Xueting Wang; Jie Ding; Xiang Zou; Peipei Jiang; Jing Du; Xiaodong Han

doi:10.1016/j.toxicon.2016.10.011

Microcystin-LR causes sexual hormone disturbance in male rat by targeting gonadotropin-releasing hormone neurons

Xueting Wang, Jie Ding, Xiang Zou, Peipei Jiang, Jing Du, Xiaodong Han

Research output: Journal article publication › Journal article › Academic research › peer-review

22 Citations (Scopus)

Abstract

The purpose of this study was to identify the target cells of MC-LR in the rat hypothalamic-pituitary axis and to investigate the underlying mechanisms. We found that the gonadotropin-releasing hormone (GnRH) neurons were the direct target of MC-LR. In vivo results showed that upon exposure to rats, cells around the third ventricle of hypothalamus underwent apoptosis. Gnrh1 expression was steadily decreased. The serum levels of GnRH, luteinizing hormone, follicle-stimulating hormone and testosterone showed a similar pattern of early-stage increase and late-stage decline. After treatment with MC-LR in immortalized hypothalamic (GT1-7) neurons, increase in cellular Ca2+and ATP resulted in downregulation of the transcriptional activators Oct-1, Otx-2, Pbx1a and Dlx2, and upregulation of the transcriptional repressor c-Jun, which may mechanistically account for the downregulation of GnRH synthesis. Ca2+and ATP could also stimulate the release of GnRH, contributing to its unique serum release pattern.

Original language	English
Pages (from-to)	45-55
Number of pages	11
Journal	Toxicon
Volume	123
DOIs	https://doi.org/10.1016/j.toxicon.2016.10.011
Publication status	Published - 1 Dec 2016
Externally published	Yes

Keywords

GnRH neuron
GT1-7 cells
Hormones
Microcystin-LR

ASJC Scopus subject areas

Toxicology

More information

10.1016/j.toxicon.2016.10.011

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title = "Microcystin-LR causes sexual hormone disturbance in male rat by targeting gonadotropin-releasing hormone neurons",

abstract = "The purpose of this study was to identify the target cells of MC-LR in the rat hypothalamic-pituitary axis and to investigate the underlying mechanisms. We found that the gonadotropin-releasing hormone (GnRH) neurons were the direct target of MC-LR. In vivo results showed that upon exposure to rats, cells around the third ventricle of hypothalamus underwent apoptosis. Gnrh1 expression was steadily decreased. The serum levels of GnRH, luteinizing hormone, follicle-stimulating hormone and testosterone showed a similar pattern of early-stage increase and late-stage decline. After treatment with MC-LR in immortalized hypothalamic (GT1-7) neurons, increase in cellular Ca2+and ATP resulted in downregulation of the transcriptional activators Oct-1, Otx-2, Pbx1a and Dlx2, and upregulation of the transcriptional repressor c-Jun, which may mechanistically account for the downregulation of GnRH synthesis. Ca2+and ATP could also stimulate the release of GnRH, contributing to its unique serum release pattern.",

keywords = "GnRH neuron, GT1-7 cells, Hormones, Microcystin-LR",

author = "Xueting Wang and Jie Ding and Xiang Zou and Peipei Jiang and Jing Du and Xiaodong Han",

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T1 - Microcystin-LR causes sexual hormone disturbance in male rat by targeting gonadotropin-releasing hormone neurons

AU - Wang, Xueting

AU - Ding, Jie

AU - Zou, Xiang

AU - Jiang, Peipei

AU - Du, Jing

AU - Han, Xiaodong

PY - 2016/12/1

Y1 - 2016/12/1

N2 - The purpose of this study was to identify the target cells of MC-LR in the rat hypothalamic-pituitary axis and to investigate the underlying mechanisms. We found that the gonadotropin-releasing hormone (GnRH) neurons were the direct target of MC-LR. In vivo results showed that upon exposure to rats, cells around the third ventricle of hypothalamus underwent apoptosis. Gnrh1 expression was steadily decreased. The serum levels of GnRH, luteinizing hormone, follicle-stimulating hormone and testosterone showed a similar pattern of early-stage increase and late-stage decline. After treatment with MC-LR in immortalized hypothalamic (GT1-7) neurons, increase in cellular Ca2+and ATP resulted in downregulation of the transcriptional activators Oct-1, Otx-2, Pbx1a and Dlx2, and upregulation of the transcriptional repressor c-Jun, which may mechanistically account for the downregulation of GnRH synthesis. Ca2+and ATP could also stimulate the release of GnRH, contributing to its unique serum release pattern.

AB - The purpose of this study was to identify the target cells of MC-LR in the rat hypothalamic-pituitary axis and to investigate the underlying mechanisms. We found that the gonadotropin-releasing hormone (GnRH) neurons were the direct target of MC-LR. In vivo results showed that upon exposure to rats, cells around the third ventricle of hypothalamus underwent apoptosis. Gnrh1 expression was steadily decreased. The serum levels of GnRH, luteinizing hormone, follicle-stimulating hormone and testosterone showed a similar pattern of early-stage increase and late-stage decline. After treatment with MC-LR in immortalized hypothalamic (GT1-7) neurons, increase in cellular Ca2+and ATP resulted in downregulation of the transcriptional activators Oct-1, Otx-2, Pbx1a and Dlx2, and upregulation of the transcriptional repressor c-Jun, which may mechanistically account for the downregulation of GnRH synthesis. Ca2+and ATP could also stimulate the release of GnRH, contributing to its unique serum release pattern.

KW - GnRH neuron

KW - GT1-7 cells

KW - Hormones

KW - Microcystin-LR

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DO - 10.1016/j.toxicon.2016.10.011

M3 - Journal article

C2 - 27773737

SN - 0041-0101

VL - 123

SP - 45

EP - 55

JO - Toxicon

JF - Toxicon

ER -

Microcystin-LR causes sexual hormone disturbance in male rat by targeting gonadotropin-releasing hormone neurons

Abstract

Keywords

ASJC Scopus subject areas

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