Responses of the medaka HPG axis PCR array and reproduction to prochloraz and ketoconazole

Effects of two model imidazole-type fungicides, prochloraz (PCZ) and ketoconazole (KTC), on the hypothalamic-pituitary-gonadal (HPG) axis of the Japanese medaka (Oryzias latipe) [corrected] were examined by use of real time PCR (RT-PCR) array. Fourteen-week-old Japanese medaka were exposed for seven days to concentrations of PCZ or KTC from 3.0 to 300 microg/L Exposure [corrected] to KTC or PCZ caused significant reduction of fecundity of Japanese medaka and down-regulated expression of estrogen receptor (ER)-alpha and egg precursors in livers of males and females. However, PCZ was more potent than KTC both in modulating transcription and causing lesser fecundity. Exposure to nominal 30 microg PCZ/L resulted in 50% less fecundity and significant down-regulation of vitellogenin II expression, but KTC did not cause such effects at this concentration. Exposure to PCZ caused a compensatory upregulation in cytochrome P450 c17alphahydroxylase, 17,20-lyase (CYP17) and aromatase (CYP19) expression in the ovary, while KTC did not. Furthermore, the ecologically relevant end point, fecundity was log-log related to mRNA level of six genes in livers of females.