Steroid D-ring glucuronides: characterization of a new class of cholestatic agents.
In summary, we have shown that steroid D-ring, but not steroid A-ring, glucuronide conjugates act at the level of the bile canaliculus to decrease bile-acid-dependent flow, initially; and subsequently, bile-acid-independent flow. These data indicate that glucuronide conjugates are not necessarily inactive; the present glucuronides clearly possess toxicological activity. The cholestatic glucuronides are all natural, endogenously formed products of metabolism. The critical questions which remain are whether metabolism of steroids to D-ring glucuronides is an obligatory step in the etiology of steroid-induced cholestasis and whether these glucuronides, at concentrations attained in humans, are capable of decreasing hepatic excretory function and inducing morphological and biochemical changes of clinical importance.
D000818:Animals; D001646:Bile / Q000187:drug effects; D001647:Bile Acids and Salts / Q000378:metabolism; D001665:Binding Sites; D002779:Cholestasis / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D004896:Erythritol / Q000378:metabolism; D005260:Female; D005965:Glucuronates / Q000633:toxicity; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000633:toxicity*; D013329:Structure-Activity Relationship
D001647:Bile Acids and Salts; D005965:Glucuronates; D013256:Steroids; D004896:Erythritol