Endocrine Abstracts

Glucocorticoid, known as cortisol, is a steroid hormone essential to the maintenance of homeostasis, and is released in response to stress and low blood glucose concentration. It is converted from cortisone by 11β hydroxysteroid dehydrogenase type 1 (11β HSD1). The liver plays a major organ in metabolism, has numerous functions, mostly consists of hepatocytes, and is a principal target of cortisol. In murine model, it was observed that too much cortisol or overexpression of 11β HSD1 induced obesity and the insulin resistance that accompanies metabolic syndrome. In our previous study, 11β HSD1-transgenic (TG) fibroblasts were established and then the porcine model was generated by SCNT using those fibroblasts. Hepatocytes overexpressing 11β HSD1 isolated from liver of this porcine model, and in vitro cultured. However, primary hepatocytes showed short life span and low proliferation rate. To overcome these problems, SV40 large T antigen, oncogene, was transduced into primary 11β HSD1-TG hepatocytes and those cells were immortalized. Immortalized 11β HSD1-TG hepatocytes shows restored morphology, more rapid proliferation rate, and more expression of 11β HSD1 than primary ones. Immortalized 11β HSD1-TG hepatocytes increase the expression of gluconeogenic genes including G6Pase and PEPCK by cortisone treatment. These immortalized cells maybe be useful for studying traits and potential pharmarcotherapeutic drugs for metabolic disorders induced by overexpression of 11β HSD1 in hepatocytes.