The Influence of Sex Hormones in Liver Function and Disease

The liver performs a multitude of bodily functions, whilst retaining the ability to regenerate damaged tissue. In this review, we discuss sex steroid biology, regulation of mammalian liver physiology and the development of new model systems to improve our understanding of liver biology in health and disease. A major risk factor for the development of liver disease is hepatic fibrosis. Key drivers of this process are metabolic dysfunction and pathologic activation of the immune system. Although non-alcoholic fatty liver disease (NAFLD) is largely regarded as benign, it does progress to non-alcoholic steatohepatitis in a subset of patients, increasing their risk of developing cirrhosis and hepatocellular carcinoma. NAFLD susceptibility varies across the population, with obesity and insulin resistance playing a strong role in the disease development. Additionally, sex and age have been identified as important risk factors. In addition to the regulation of liver biochemistry, sex hormones also regulate the immune system, with sexual dimorphism described for both innate and adaptive immune responses. Therefore, sex differences in liver metabolism, immunity and their interplay are important factors to consider when designing, studying and developing therapeutic strategies to treat human liver disease. The purpose of this review is to provide the reader with a general overview of sex steroid biology and their regulation of mammalian liver physiology.

Automated summary

This review discusses the biology of sex steroids, regulation of mammalian liver physiology, and the development of new model systems to enhance understanding of liver biology in health and disease. Hepatic fibrosis is a major risk factor for liver disease, driven by metabolic dysfunction and pathological immune activation. Non-alcoholic fatty liver disease (NAFLD) can progress to non-alcoholic steatohepatitis, increasing the risk of cirrhosis and hepatocellular carcinoma. Obesity and insulin resistance, as well as sex and age, are important risk factors for NAFLD. Sex hormones also play a role in regulating liver metabolism and the immune system, emphasizing the importance of considering sex differences in liver disease treatment strategies.