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

Gen Comp Endocrinol. 2011 Dec 1;174(3):309-17. doi: 10.1016/j.ygcen.2011.09.008. Epub 2011 Sep 22.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

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 Proteins / genetics*
  • Zebrafish Proteins / metabolism
  • Zebrafish* / genetics
  • Zebrafish* / metabolism

Substances

  • Antifungal Agents
  • Zebrafish Proteins
  • Testosterone
  • Steroid 17-alpha-Hydroxylase
  • cyp17a1 protein, zebrafish
  • Clotrimazole
  • 11-ketotestosterone