Estrogen-induced hepatic toxicity and hepatic cancer: differences between two closely related hamster species

Estrogen is known to affect hepatobiliary function; however, it is unusual for high serum levels of estrogen to actually result in clinically detectable hyperbilirubinemia. Women affected by cholestatic jaundice during pregnancy share this genetic susceptibility with two Cricetulus hamsters, the Armenian hamster (Cricetulus migratorius) and the Chinese hamster (Cricetulus griseus). Nevertheless, the pathophysiologic process responsible for this estrogen induced icterus may be different in women and hamsters. The present study compares various facets of estrogen-induced icterus in these two closely related hamsters.

Hamsters were injected with various estrogens and the acute and chronic effects on liver were monitored by measuring changes in serum constituents and by observing changes in hepatic structure as seen grossly and by light and electron microscopy.

In previous studies, hepatic tumors developed in most Armenian hamsters after chronic estrogen treatment, but in the present study, the livers of Chinese hamsters were remarkably free of neoplastic change under similar conditions. Also, when compared with the responses in the Armenian hamsters, signs of hepatic destruction and regeneration were less prevalent in estrogen-treated Chinese hamsters, and they were less susceptible to the effects of estrogen (because larger doses of estrogen were required to produce icterus and the bilirubin levels were lower and of shorter duration). In contrast to the findings in Armenian hamsters, bile canaliculi were severely affected in livers of estrogen-treated Chinese hamsters, and hepatic microvesicular steatosis, indicative of an unusual lipodystrophy caused by estrogen, was prominent. An additional lesion peculiar to the Chinese hamster was striking sinusoidal dilatation, which may be analogous to the oral contraceptive-induced sinusoidal dilatation in humans.

Although these two hamster species are genetically similar, the genes activated by the estrogen receptor show remarkable heterogeneity when their respective livers are examined. Comparisons within these species may provide information about the specific gene activation responsible for particular pathologic events.