Mechanisms of action underlying the antiandrogenic effects of the fungicide prochloraz

These results indicate that reduced activity of P450c17 may be a primary cause of the disrupted fetal steroidogenesis and that an altered androgen metabolism may play a role as well

Peter Laier; Stine Broeng Metzdorff; Julie Borch; Marie Louise Hagen; Ulla Hass; Sofie Christiansen; Marta Axelstad; Thuri Kledal; Majken Dalgaard; Chris McKinnell; Leon J.S. Brokken; Anne Marie Vinggaard

2006

Scholarcy highlights

  • The fungicide prochloraz has got multiple mechanisms of action that may influence the demasculinizing and reproductive toxic effects of the compound
  • Caesarian sections were performed on selected dams at gestational day 21, while others were allowed to give birth to pups that were followed until postnatal day 16
  • Immunohistochemistry of fetal testes showed increased expression of 17α-hydroxylase/17,20-lyase and a reduction in 17β-hydroxysteroid dehydrogenase expression, whereas no changes in expression of genes involved in testicular steroidogenesis were observed
  • Increased expression of P450c17 mRNA was observed in fetal male adrenals, and the androgen-regulated genes ornithine decarboxylase, prostatic binding protein C3 as well as insulin-like growth factor I mRNA were reduced in ventral prostates PND 16
  • These results indicate that reduced activity of P450c17 may be a primary cause of the disrupted fetal steroidogenesis and that an altered androgen metabolism may play a role as well
  • In vitro studies on human adrenocortical carcinoma cells supported the findings in vivo as reduced testosterone and increased progesterone levels were observed. These results together indicate that prochloraz acts directly on the fetal testis to inhibit steroidogenesis and that this effect is exhibited at protein, and not at genomic, level

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