Sex-Dependent Claudin-1 Expression in the Liver of Euthyroid and Hypothyroid Mice

In the liver the tight junction protein claudin-1 plays an important role in bile secretion by maintaining the paracellular barrier of bile canaliculi and the bile duct. A diminished bile excretion has been found in hypothyroid patients, and the prevalence of gallstones is increased in hypothyroidism. This association, however, only applies for men and is in contrast to the well-established female preponderance of biliary disease in the general population.

We hypothesized that hypothyroidism could lead to altered claudin-1 expression in the liver, and that this effect may be sex specific.

We characterized claudin-1 expression and localization in livers of euthyroid and hypothyroid male and female C57BL/6NTac mice by real-time PCR, Western blot and immunofluorescence.

Claudin-1 is expressed in canalicular regions and the bile ducts of the murine liver. Livers of female mice showed lower claudin-1 expression than male livers. In hypothyroid livers, female animals showed an elevated claudin-1 expression, whereas reduced claudin-1 expression was found in male animals compared to the euthyroid controls.

We demonstrate a correlation between claudin-1 expression and hypothyroidism in the murine liver. Furthermore, a sex-dependent alteration of claudin-1 expression was found.