BETA-NAPHTHOFLAVONE ABOLISHES INTERRENAL SENSITIVITY TO ACTH STIMULATION IN RAINBOW-TROUT

We report for the first time that beta-naphthoflavone (BNF) abolishes ACTH stimulation of cortisol production in rainbow trout (Oncorhynchus mykiss). There was significantly higher hepatic cytochrome P450 conte nt and ethoxyresorufin O-de-ethylase and uridine-5'-diphosphoglucuroni c acid transferase activities in BNF-treated fish than in sham-treated controls. BNF did not significantly effect either plasma turnover or tissue distribution of [H-3]cortisol-derived radioactivity. Hepatic me mbrane fluidity and hepatocyte capacity for cortisol uptake were not a ltered by BNF as compared with the sham-treated fish. These results ta ken together suggest that BNF does not affect cortisol-clearance mecha nisms in trout. A 3 min handling disturbance period elicited a plasma cortisol response in the sham-treated fish; however, the response in t he BNF-treated fish was muted and significantly lower than in the sham fish. This in vivo response corroborates the lack of interrenal sensi tivity to ACTH in vitro in the BNF-treated fish, suggesting that BNF a ffects the ACTH pathway in trout. Our results suggest the possibility that cytochrome P450-inducing compounds may affect cortisol dynamics b y decreasing interrenal responsiveness to ACTH stimulation in fish, th ereby impairing the physiological responses that are necessary for the animal to cope with the stressor.