Testosterone enhances taurine synthesis by upregulating androgen receptor (AR) and cysteine sulfinic acid decarboxylase (CSAD) expression in male mouse liver.

Taurine is an end-product of cysteine metabolism, while cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSAD) are key enzymes regulating taurine synthesis. Sex steroids, including estrogens and androgens, are associated with liver physio-pathological processes, however, we still do not know whether taurine and sex steroids interact in regulating liver physiology and hepatic diseases, and whether there are sex differences although our recent study shows the estrogen is involved in regulating taurine synthesis in mouse liver. The present study was thus proposed to identify whether 17-beta estradiol and testosterone play their roles by regulating CDO and CSAD expression and taurine synthesis in male mouse liver. Our results demonstrated that testosterone did not have significant influence on CDO expression, but significantly enhanced CSAD, androgen receptor (AR) expressions and taurine levels in mouse liver, cultured hepatocytes and HepG2 cells, whereas these effects were abrogated by AR antagonist flutamide. Further, our results showed that testosterone increased CSAD-promoter-luciferase activity through direct interacting of AR DNA binding domain with CSAD promoter. These findings firstly demonstrate that testosterone acts as important factor to regulate sulfur amino acid metabolism and taurine synthesis through AR/CSAD signaling pathway. In addition, the in vivo and in vitro experiments showed that 17-beta estradiol has no significant effects on liver CSAD expression and taurine synthesis in male mice and suggest that the effects of sex steroids on the taurine synthesis in mouse liver has sex differences. These results are crucial for understanding the physiological functions of taurine/androgen and their interacting mechanisms in liver.