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

Abstract

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.

Effect of estrogen on scavenger receptor BI expression in the rat

“…No significant changes in body weight were apparent at 2 days in rats treated with estrogen alone or estrogen plus dexamethasone. A significant decrease in body weight was seen in all animals treated with estrogen at the 5-day time point (Table 2, P<0·05), which is similar to previous reports (Hornstein et al 1992).…”

“…Estrogen treatment is associated with a flattening of the microvilli, resulting in a 43% decrease in the sinusoidal surface area and a 50% decrease in sinusoidal volume (Hornstein et al 1992). Moreover, high-dose estrogen treatment is associated with a 15-fold increase in circulating bile acids (Hornstein et al 1992), which also may affect the lipid composition and fluidity of hepatocyte membranes. Since much of the hepatic SR-BI resides in the plasma membrane, its half-life may be affected by these changes.…”

Cholestasis-induced alterations of the trans- and paracellular pathways in rat hepatocytes

“…Junctional length per cubic centimetre of liver decreases slightly following EE treatment, but increases significantly after BDL. Since EE treatment is known to increase liver volume (Hornstein et al 1992) normalization of the data to body weight reveals a marked increase in junctional length in both cholestatic groups. The degree of alteration again follows the sequence: control<EE<BDU In summary, these data support the view that EE treatment leads to TJ defects that are less severe than those induced by BDL.…”

Protective effect of Jasonia montana against ethinylestradiol-induced cholestasis in rats

“…The mechanism by which EE induces cholestasis is still unclear although interference with bile salt-independent bile flow (Guevas et al, 2001) and reduced capacity of hepatocytes to excrete organic anions and cholephilic compounds has been suggested (Alvaro et al, 1997). EE treatment is also associated with several hepatocellular changes, which include decreased plasma membrane fluidity, decreased Na + -K + -ATPase (Simon et al, 1996) and substantial decreased in the volume density of sinusoidal microvilli and the sinusoidal plasma membrane surface density (Hornstein et al, 1992). Chronic cholestatic liver diseases, including primary biliary cirrhosis, extrahepatic biliary arresia, idiopathic adulthood ductopenia, primary sclerosing cholangitis, idiopathic neonatal hepatitis, Byler's disease and arteriohepatic dysplasia, are leading indications for liver transplantation (Kim et al, 2000).…”