Ventolin Inhalers

- Late Gestational Exposure to the Fungicide Prochloraz: DISCUSSION(2)

In the current study, we also demonstrated that in vitro PZ competed with a high-affinity synthetic androgen to bind to rat AR and that PZ also inhibited DHT-induced human AR-dependent gene expression at concentrations that did not induce cytotoxicity. Such results support the hypothesis that in vitro, PZ exhibits antiandrogenic activity by competing with androgens for receptor sites and support prior reports of PZ inhibition of AR transactivation. These results and findings from our laboratory demonstrating that PZ also inhibits fetal androgen production indicate that PZ could interfere with the androgen signaling pathway during sexual differentiation via two independent mechanisms (i.e., by acting as an AR antagonist and by inhibiting testosterone synthesis).

The AR affinity of PZ may distinguish it from other imidazole-like compounds. Although the imidazole-like compounds PZ, bifonazole, clotrimazole, econazole, isoconazole, ketoconazole, miconazole, and tioconazole all inhibit 17,20 lyase activity in testicular or adrenal microsomes, only PZ is an AR antagonist. We also observed that PZ delayed parturition at all dosage levels, an effect consistent with in vitro studies, demonstrating that PZ inhibits CYP19 aromatase, the enzyme required for estrogen synthesis.

April 12, 2014 Parturition
Tags: antiandrogen environment fungicide hypospadias male reproductive tract