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Enzymatic sulfation of steroids 20. effects of 10 drugs on the hepatic glucocorticoid sulfotransferase activity of rats in vitro and in vivo


, : Enzymatic sulfation of steroids 20. effects of 10 drugs on the hepatic glucocorticoid sulfotransferase activity of rats in vitro and in vivo. Biochemical Pharmacology 33(21): 3485-3490

The effects of 10 drugs on hepatic glucocorticoid sulfotransferase activity (HGSTA) were examined in male rats. The enzyme activity per 100 g body wt was elevated 152, 94.9, 140, 140, 73.1, 63.9, 76.9, and 140% after administration of daily i.p. doses of 111 mg spironolactone/kg (6-10 days), 66.7 mg WIN-24540 [trilostane]/kg (6-10 days), 150 mg metyrapone/kg (19-31 days), 33.3 mg pentachlorophenol/kg (9-16 days), 16.5 mg aspirin/kg (10-16 days), 90.5 mg alloxan/kg (23-27 days), 104 mg aminoglutethimide/kg (12-20 days), and 16.8 mg propranolol/kg (21-27 days). Shorter experimental periods or lower drug doses caused smaller effects on HGSTA. Most notably, spironolactone (111 mg/kg) and WIN-24540 (66.7 mg/kg) caused 50-75% elevation of HGSTA in 2 days. Effects of WIN-24540, aspirin and pentachlorophenol were due mostly to elevation of hepatic levels of sulfotransferase III (STIII), the glucocorticoid-preferring sulfotransferase of rat liver. Effects of the other test drugs were due to elevation of hepatic levels of sulfotransferases I and II (STI and STII), which much prefer dehydroepiandrosterone as substrate, but also catalyze glucocorticoid sulfation. Enzyme inhibition studies showed that the test drug interacted with the HGSTA in vitro in a fashion that appeared to be related to the in vivo effects already described. None of the drugs interacted exclusively with STI, STII or STIII in vitro. However, some differences of the strengths of individual drug-sulfotransferase interactions were observed. The drug effects are discussed in relation to drug and glucocorticoid actions. [Theophylline and cortisol were also used.].

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