Sex hormones regulate hepatic fetuin expression in male and female rats

Background: To date, there are limited studies on the sex-specific relationship between fetuins (Ft-A and Ft-B) and metabolic diseases. Our recent proteomic study has shown that fetuins may play sex-dependent roles in obesity and diabetes. In the present study, we investigated the expression of hepatic fetuins with respect to the effects of sex hormones both in vivo and in vitro. Methods & Results: A sex hormone-treated rat model was established in order to study the effects of sex hormones on hepatic fetuin expression. Animal experiments revealed that 17β-estradiol (E2)- and dihydrotestosterone (DHT)-treated rats showed opposite effects in terms of body weight gain in both genders. Interestingly, Ft-A and Ft-B were sex-dependently expressed in the livers of rats, responding to different regulatory modes of sex hormone receptors (ERα, ERβ, and AR). To validate in vivo data, rat normal liver cells were treated with E2 or DHT at different concentrations, and similar expression patterns as those in the animal-based experiments were confirmed. We found that these changes were mediated via sex hormone receptors using antagonist experiments. Conclusion: The results of the present study indicate that sex hormones induce gender-dimorphic expression of hepatic fetuins directly via sex hormone receptors. To the best of our knowledge, this is the first approach to address the effects of sex hormones on hepatic fetuin expression.