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 | |
| Publication status | Published - 1 Dec 2016 |
| Externally published | Yes |
Keywords
- GnRH neuron
- GT1-7 cells
- Hormones
- Microcystin-LR
ASJC Scopus subject areas
- Toxicology