| Autor: |
Davis RA, Elliott TS, Lattier GR, Showalter RB, Kern F Jr |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemistry [Biochemistry] 1986 Apr 08; Vol. 25 (7), pp. 1632-6. |
| DOI: |
10.1021/bi00355a028 |
| Abstrakt: |
Rats treated with ethinylestradiol (5 mg kg-1 day-1 for 5 days) secrete de novo synthesized bile acids at a markedly reduced rate (-57%). Administration of the nonionic detergent Triton WR-1339 to estradiol-treated rats rapidly restored the rate of secretion of de novo synthesized bile acids to control levels. In contrast, when Triton was administered to control rats, the secretion rate of bile acids was unaffected. The reduction in bile acid synthesis displayed by estradiol-treated rats was similar to the 50% decrease in the activity of hepatic microsomal 7 alpha-hydroxylase. The activity of 7 alpha-hydroxylase was also restored to control levels by the administration of Triton to estradiol-treated rats. We examined the possibility that estradiol acts directly on the hepatic microsomes. Adding increasing amounts of estradiol to microsomes obtained from control rats resulted in decreasing activities of 7 alpha-hydroxylase. The inhibition by estradiol of 7 alpha-hydroxylase obtained in vitro occurred with amounts of estradiol that were found to accumulate in the liver via in vivo treatment. Double-reciprocal analysis showed that at and below 50 micrograms of estradiol/0.5 mg of protein uncompetitive inhibition was displayed. Additional experiments showed that adding Triton to microsomes obtained from estradiol-treated rats increased the activity of 7 alpha-hydroxylase to control levels. In contrast, Triton did not increase the activity of 7 alpha-hydroxylase when it was added to control microsomes. These data show for the first time that the estrogenic steroid estradiol acts directly on the microsomes and inhibits both the activity of 7 alpha-hydroxylase and the rate of bile acid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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