Organ specific regulation of sterol 14-demethylase P450 expression relating to its organ specific functions

点击翻译按钮获取中文摘要

This subject consists of a part of our research project for examining organ specific regulatory mechanisms of sterol 14-demethylase P450(CYP51) expression relating to its organ specific functions. CYP51 is a unique P450 that expresses ubiquitously in mammalian organs. However, its expression level was considerably different among organs, suggesting that expression of CYP51 might be regulated differently by organ specific manners. Then, effects of several hormones on the CYP51 expression levels in liver, small intestine, adrenal gland, brain and ovary of rats were examined. The most interesting finding was specific induction of ovarian CYP51 by a gonadotropin(PMSG). Since 14-demethylated derivatives of lanosterol have been identified as mammalian meiosis activating sterols(MAS), the gonadotropin dependent expression of ovarian CYP51 might be related to this ovary specific function of CYP51. The immunohistochemical observation indicating that the gonadotropin-dependent expression of CYP5 … More 1 was localized at tumulus and granulosa cells close to oocyte supported this possibility. The expression of hepatic CYP51 was dependent on insulin. The enhancing effect of insulin was explained by its inducing effect on SREBP-1c, as in the case of other lipid metabolizing enzymes. This fact indicated that the expression of hepatic CYP51 might be regulated as a member of lipid-metabolizing enzymes. It was also shown that expression of CYP51 in liver, small intestine and adrenal gland was dependent on thyroid hormone. The thyroid hormone-dependent expression of CYP51 was repressed by dexamethazone(dex), and dex reduced the CYP51 contents in liver, small intestine and adrenal gland. Dose response experiments suggested the contribution of glucocorticoid receptor to the repressive effect of dex on CYP51 expression. No substantial difference was observed between the hormonal regulation of CYP51 expression in brain and liver. Essential role of SER,CRE and a GCAAT element on CYP51 expression was also suggested. Less