Estradiol And Testosterone Regulate Taurine Content And Its Biosynthetic Enzymes Expression In Mice Liver

Cysteine sulfinic acid decarboxylase (CSAD) is the rate-limiting enzyme in taurine de novo synthesis and it has some functions in the physiology and pathology of the liver, its expression is associated with estradiol and testosterone concentration. The present study was designed to determine the relation between estradiol, testosterone and taurine in murine liver.In the female mice, We initially observed the mice had lower levels of CSAD, CDO and taurine during estrus than diestrus. We then respectively treated the ovariectomized mice, the cultured hepatocytes, and HepG2cells with different doses of E2, and the CSAD, CDO expressions and taurine levels were analyzed. The results showed that E2decreased taurine level in the serum and the cultured cells by inhibiting CSAD and CDO expressions. Further, we identified the molecular receptor types through which E2plays its role in regulating taurine synthesis, and our results showed that estrogen receptor-alpha (ERa) expression was much higher than estrogen receptor-beta (ERβ) in the liver and hepatocytes, and the inhibiting effects of E2on CSAD, CDO and taurine level were partially abrogated in the ICI182,780pretreated liver and hepatocytes, and in ERa knockout mice. These results indicate that estradiol decreases taurine content by reducing taurine biosynthetic enzymes expression in mice liver.The results in male mice demonstrated that T significantly increased the CSAD mRNA, protein levels and CDO protein expression, but had no obvious effect on the mRNA expression of CDO in the emasculated liver, cultured hepatocytes and HepG2cells. Besides that, we also demonstrated those effects of T were partially abrogated by the pretreatment with androgen receptor (AR) antagonist flutamide (F). The further luciferase results showed T increased CSAD activity (-1919/+29) only when AR was co-transfected.Finally, increased intracellular reactive oxygen species (ROS) levels were detected in CSAD overexpressed HepG2cells and293FT cells. These results indicate that estradiol decreases taurine concentrations by reducing CSAD through ERa in female mice liver and testosterone enhance taurine biosynthesis enzymes expressions. Besides that, we also found that CSAD levels are positively associated with intracellular ROS levels.Taken together, these results indicate that the concentrations of taurine and taurine biosynthetic enzymes expression are close connected with sex hormones levels in the liver and those fuction of sex hormones are rely on their receptors.Besides that, taurine biosynthetic enzymes expression are close connected with intracellular ROS levels.