In vivo alternative assessment of the chemicals that interfere with anterior pituitary POMC expression and interrenal steroidogenesis in POMC:EGFP transgenic zebrafish

Sun, L., Xu, W., He, J., and Yin, Z.
Toxicology and applied pharmacology   248(3): 217-225 (Journal)
Registered Authors
He, Jiangyan, Yin, Zhan
Endocrine disruption, Zebrafish, POMC:EGFP transgenic line, Interrenal development
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Fluorescent Dyes
  • Gene Expression Regulation/drug effects
  • Green Fluorescent Proteins/biosynthesis*
  • Green Fluorescent Proteins/genetics
  • Interrenal Gland/drug effects
  • Interrenal Gland/metabolism*
  • Organophosphorus Compounds/toxicity*
  • Pituitary Gland, Anterior/drug effects*
  • Pituitary Gland, Anterior/metabolism
  • Pituitary Hormones, Anterior/antagonists & inhibitors
  • Pituitary Hormones, Anterior/biosynthesis
  • Pro-Opiomelanocortin/antagonists & inhibitors
  • Pro-Opiomelanocortin/biosynthesis*
  • Zebrafish/genetics*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/biosynthesis*
20732339 Full text @ Tox. App. Pharmacol.
Adrenocorticotropin (ACTH) has been considered a classic adrenocorticotropic hormone and the key pituitary-derived peptide controlling steroidogenesis in the adult adrenal. ACTH is encoded by the propiomelanocortin (POMC) gene, and its active form is mainly synthesized and processed from the POMC-encoded multi-hormone precursor in the anterior pituitary. The ACTH level has always been precisely controlled in the signaling cascade of the hypothalamo-pituitary-adrenal (HPA) axis due to its central role. The purpose of this study was to investigate whether the transgenic zebrafish line with EGFP driven by the POMC promoter can be used as a surrogate marker to detect the interference effects on anterior pituitary POMC expression caused by chemicals in teleost. The Tg (POMC:EGFP) fish treated for 4days with the known adrenergic agents, dexamethasone (Dex) or aminoglutethimide (AG), exhibited altered levels of EGFP and POMC expression in the anterior domain of pituitary corticotrophs. Whole-mount in situ hybridization revealed impaired patterns of expression of the zebrafish ftz-fl gene (ff1b), a key molecular marker for early interrenal development. Next, several chemicals and six commonly used organophosphorus compounds (OPs) were tested for their effects on anterior pituitary POMC expression and early interrenal development. Our preliminary screening analyses indicated that simazine and 3,3',4,4'5-pentachlorobiphenyl (PCB126) could interfere with anterior pituitary POMC expression and interrenal development in fish. In summary, our results demonstrated that the Tg (POMC:EGFP) zebrafish line might be employed as a specific and reproductive in vivo assessment model for the effects of endocrine disruption on HPA signaling.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes