PUBLICATION

Characterization of testicular expression of P450 17α-hydroxylase, 17,20-lyase in zebrafish and its perturbation by the pharmaceutical fungicide clotrimazole

Authors
Hinfray, N., Baudiffier, D., Leal, M.C., Porcher, J.M., Aït-Aïssa, S., Le Gac, F., Schulz, R.W., and Brion, F.
ID
ZDB-PUB-111019-8
Date
2011
Source
General and comparative endocrinology   174(3): 309-17 (Journal)
Registered Authors
Le Gac, Florence, Schulz, Rüdiger W.
Keywords
zebrafish, steroidogenesis, cyp17a1, pharmaceutical, clotrimazole, testis culture
MeSH Terms
  • Animals
  • Antifungal Agents/pharmacology
  • Brain/drug effects
  • Brain/enzymology
  • Brain/metabolism
  • Cells, Cultured
  • Clotrimazole/pharmacology*
  • Female
  • Gene Expression Regulation, Enzymologic/drug effects*
  • Gonads/drug effects
  • Gonads/enzymology
  • Gonads/metabolism
  • Male
  • Primary Cell Culture
  • Steroid 17-alpha-Hydroxylase/genetics*
  • Steroid 17-alpha-Hydroxylase/metabolism
  • Testis/chemistry
  • Testis/drug effects*
  • Testis/enzymology*
  • Testis/metabolism
  • Testosterone/analogs & derivatives
  • Testosterone/metabolism
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
PubMed
21963961 Full text @ Gen. Comp. Endocrinol.
Abstract
The aim of the present study was to characterize P450 17α-hydroxylase/17,20-lyase (cyp17a1) expression in zebrafish and to assess the effect of the pharmaceutical clotrimazole, a known inhibitor of various cytochrome P450 enzyme activities, on testicular gene and protein expression of this enzyme as well as on the testicular release of 11-ketotestosterone (11-KT), a potent androgen in fish. We first showed that cyp17a1 is predominantly expressed in gonads of zebrafish, notably in male. In vivo, clotrimazole induced a concentration-dependent increase of cyp17a1 gene expression and Cyp17-I protein synthesis in zebrafish testis. Using zebrafish testicular explants, we further showed that clotrimazole did not directly affect cyp17a1 expression but that it did inhibit 11-KT release. These novel data deserve further studies on the effect of azole fungicides on gonadal steroidogenesis.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping