Ethinylestradiol increases volume and decreases sinusoidal membrane surface in the rat liver: a stereological analysis.

Structural alterations of liver parenchyma caused by ethinylestradiol, a synthetic estrogen known to induce cholestasis and to act as a tumor promoter factor, were investigated. Male rats treated with 17 alpha-ethinylestradiol (5 mg/kg body weight for 5 days) were compared with controls (n = 5 each). After perfusion fixation and systematic random sampling, paraffin sections, semithin sections and thin sections were examined observing standard stereological techniques. Ethinylestradiol treatment induced an increase in liver volume by 65% (p less than 0.001), which was caused more by hypertrophy (volume of singular hepatocyte +35%, p less than 0.001) than by hyperplasia (number of hepatocytes +23%, p less than 0.001). A decrease in sinusoidal membrane surface density (-43%, p less than 0.005) associated with a decrease in sinusoidal microvillar volume density (-50%, p less than 0.005) were both compensated for by the increase in liver volume. No canalicular alterations were observed. Thus changes in hepatocytes detectable with stereological techniques affect the sinusoidal pole where decreased sinusoidal membrane surface is associated with or reflects a substantial loss of membrane phospholipids. The increased liver volume may constitute an adaptive response compensating for the relative decrease in sinusoidal membrane surface and displays characteristics comparable to those of preneoplastic hepatocytes.