Estrogen induces cytokeratin aggregation in primary cultures of Armenian hamster hepatocytes

Abstract

The effect of estrogen administration to cultured Armenian hamster was studied. Isolated Armenian hamster hepatocytes were cultured in RPMI medium supplemented with beta-estradiol (E2). Beta-estradiol treatment for 24-48 hr induced cytoplasmic inclusion bodies which by immunocytochemistry were positive for cytokeratin (CK) 8, CK 18, and ubiquitin but negative for CK 7 and CK 19. These inclusion bodies appeared as filamentous tangles or amorphous aggregates when observed by electron microscopy. F-actin, tubulin, and desmosomes were not influenced by the presence of the inclusion bodies. Addition of ethanol to culture medium increased the incidence of the inclusion formation. In combination with 0.5% ethanol 1 microM of E2 induced five to six times more inclusion bodies, while the number of inclusion bodies decreased when epidermal growth factor (EGF) was added to the medium in combination with E2. This reduction effect was nullified by treatment with anti-EGF receptor antibody. These findings suggest that E2 treatment to Armenian hamster hepatocytes in vitro induces Mallory body-like inclusions whose incidence can be influenced by addition of ethanol or EGF to the culture medium.