Inhibition of rat and human steroidogenesis by triazole antifungals

Systems Biology in Reproductive Medicine
Amber K GoetzDavid J Dix

Abstract

Environmental chemicals that alter steroid production could interfere with male reproductive development and function. Three agricultural antifungal triazoles that are known to modulate expression of cytochrome P450 (CYP) genes and enzymatic activities were tested for effects on steroidogenesis using rat in vivo (triadimefon), rat in vitro (myclobutanil and triadimefon), and human in vitro (myclobutanil, propiconazole, and triadimefon) model systems. Hormone production was measured in testis organ cultures from untreated adult and neonatal rats, following in vitro exposure to 1, 10, or 100 muM of myclobutanil or triadimefon. Myclobutanil and triadimefon reduced media levels of testosterone by 40-68% in the adult and neonatal testis culture, and altered steroid production in a manner that indicated CYP17-hydroxylase/17,20 lyase (CYP17A1) inhibition at the highest concentration tested. Rat to human comparison was explored using the H295R (human adrenal adenocarcinoma) cell line. Following 48 h exposure to myclobutanil, propiconazole, or triadimefon at 1, 3, 10, 30, or 100 muM, there was an overall decrease in estradiol, progesterone, and testosterone by all three triazoles. These data indicate that myclobutanil, propiconazole, an...Continue Reading

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Citations

May 28, 2013·Archives of Toxicology·Wiebke PrutnerPablo Steinberg
Jan 24, 2013·Environmental Science and Pollution Research International·Damien BaudiffierFrançois Brion
Mar 3, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Sanne A B HermsenAldert H Piersma
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Oct 6, 2020·Frontiers in Pharmacology·Zackary MontoyaSang-Hyuck Park
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Aug 18, 2020·Ecotoxicology and Environmental Safety·Yosra Ben OthmèneChristophe Lemaire

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