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 publicationJournal articleAcademic researchpeer-review

10 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 languageEnglish
Pages (from-to)45-55
Number of pages11
JournalToxicon
Volume123
DOIs
Publication statusPublished - 1 Dec 2016
Externally publishedYes

Keywords

  • GnRH neuron
  • GT1-7 cells
  • Hormones
  • Microcystin-LR

ASJC Scopus subject areas

  • Toxicology

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