Diethylstilbestrol-Induced Jaundice in the Chinese and Armenian Hamster

Abstract

An unusual and impressive hyperbilirubinemia was induced in Chinese hamsters by administration of diethylstilbestrol (DES). This icterus was dose-dependent and affected females more severely than males. However, a similar mortality was detected in both sexes. Another hamster, the Armenian hamster, was even more susceptible to the icteric and lethal effects of DES. The hamster model of DES-induced icterus showed many clinical dissimilarities when compared to the human estrogen-induced jaundice, simple cholestatic jaundice. Furthermore, hepatic pathology was distinctly different as canalicular cholestasis was absent although other degenerative and regenerative hepatocellular changes were present. Livers of Armenian hamsters were more severely affected than were livers from Chinese hamsters and contained Mallory bodies even within 1 week after DES treatment. A modest, nonlethal jaundice also was detected in European hamsters after DES injection, whereas Syrian hamsters were not affected even after larger doses. This unique sensitivity to DES, and the spectrum of sensitivity within these related hamsters (Armenian > Chinese > European vs. resistant Syrian) provide an interesting model for study of DES effect on hepatic function.Idiopathic jaundice of pregnancy and more recently, jaundice associated with oral contraceptives are two human diseases in which hepatic function is clinically impaired by estrogenic components (1, 2). A genetic predisposition is apparently necessary and responsible for this estrogen-induced jaundice (3, 4), although a minor impairment of biliary excretion can be detected (by bromosulfophthalein excretion, etc.) in normal patients receiving estrogens (5) or in late pregnancy (61, and this estrogen effect is enhanced in the diseased liver (7). Hepatic injury has been reported occasionally in human males treated with synthetic estrogen therapy [ stilbestrol or diethylstilbestrol (DES)] for prostatic carcinoma. Such injury has been manifested by abnormalities of tests of hepatic function (8), jaundice with intrahepatic cholestasis (9-13), alcoholic hepatis-like injury (14), and peliosis hepatitis (13, 15). A case of hepatocellular jaundice resulting from an allergic reaction to DES also has been reported (16).Early studies on toxic effects from administration of natural and synthetic estrogens indicated the presence of hepatotoxicity (fatty degeneration and interstitial hepatitis) although a species susceptibility (dog vs. rat) was quite distinct (17-19). In various experimental animal models, injection of estrogens has been shown to impair biliary excretion (as measured by bromosulfophthalein) (20-22) but the production of severe hepatic dysfunction was uncommon. The present report defines the extraordinary jaundice and hepatic pathology induced by DES in the Chinese hamster. This novel response to DES was even more impressive in the Armenian hamster and present to some degree in the European hamster. On the other hand, Syrian hamsters were not affected even after larger doses of DES. Although t...