Disruption of Rapid, Nongenomic Steroid Actions by Environmental Chemicals: Interference with Progestin Stimulation of Sperm Motility in Atlantic Croaker

摘要

Several nongenomic steroid actions, like genomic ones, can be disrupted by estrogenic xenobiotics (xenoestrogens), but the extent and sensitivity of this alternative mechanism of steroid action to chemical interference remain unclear. The effects of environmentally realistic concentrations of a broad range of organic contaminants on the nongenomic action of a progestin (17,20β,21 -trihydroxy-4-pregnen-3-one or 20β-S) to upregulate Atlantic croaker sperm motility were examined in an in vitro bioassay. Pretreatment of sperm for 10 min in vitro with estrogenic compounds (estradiol-17β, o,p'-DDT derivatives, zearalenone, bisphenol A, 2',3',4',5'-PCB-4-OH, kepone, chlordane, methoxyclor) and nonestro-genic organic compounds (p,p'-DDT derivatives, atrazine, Aroclor 1254, naphthalene, benzene) at concentrations ranging from 0.01 to 10 μM did not decrease the percent of motile sperm, but all of them partially or completely blocked the response to 20β-S. Most of the compounds impaired this endocrine mechanism at a concentration of 0.1μM (～30- 40ppb), whereas o,p'-DDT and atrazine were effective at lower concentrations. The antagonistic actions of o,p'-DDT were partially reversed with 10-fold higher concentrations of 20β-S, which is consistent with a hormone receptor-mediated mechanism of DDT action. The finding that low concentrations of a wide range of organic environmental contaminants can interfere with a rapid, nongenomic steroid action suggests that this mechanism of endocrine disturbance is of toxicological importance.