Kidney 11 beta-HSD2 is inhibited by glycyrrhetinic acid-like factors in human urine

被引:24
作者
Lo, YH
Sheff, MF
Latif, SA
Ribeiro, C
Silver, H
Brem, AS
Morris, DJ
机构
[1] BROWN UNIV,MIRIAM HOSP,DEPT PATHOL & LAB MED,SCH MED,WOMAN & INFANTS HOSP,PROVIDENCE,RI 02906
[2] BROWN UNIV,RHODE ISL HOSP,SCH MED,PROVIDENCE,RI 02906
关键词
licorice; hydroxysteroid dehydrogenase glycyrrhetinic acid; urine; GALF; pregnancy;
D O I
10.1161/01.HYP.29.1.500
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
We have previously shown that human urine contains substances that, like glycyrrhetinic acid, inhibit 11 beta-HSD1. We have named these substances ''glycyrrhetinic acid-like factors'' or GALFs. We now have found that human urine contains measurable quantities of both 11 beta(HSD1)- and 11 beta(HSD2)-GALF inhibitory substances. Both are markedly elevated in pregnancy. Their chemical and high-performance liquid chromatography (HPLC) characteristics suggest that several of the GALFs are steroidal. Large quantities of neutral 11 beta(HSD1)- and 11 beta(HSD2)-GALFs can be extracted directly from urine into ethyl acetate, yielding fraction EA(1). Hydrolysis of the GALFs remaining in the aqueous phase by beta-glucuronidase markedly increases the total amounts of GALFs, with the majority now being ethyl acetate extractable (fraction EA(2)). These EA(2) post-hydrolysis GALFs can be separated by HPLC resulting in at least six components with inhibitory activity against each isoenzyme. Only two GALF peaks are active against both 11 beta-HSD1 and 11 beta-HSD2. The others are peaks with specific 11 beta(HSD 1)- and 11 beta(HSD2)-GALF inhibitory activity. The GALFs in the same posthydrolysis EA1 extract are also inhibitory toward the 11 beta HSD1 that is present in vascular smooth muscle where they may play a role in the mechanisms controlling blood pressure. We have also found that 11 beta-HSD2 is selectively inhibited by 5 alpha-(but not by 5 beta-) reduced steroids. GC-MS analysis of the 11 beta(HSD2)-GALFs in EA(2) is now being performed to determine whether this group includes 3 alpha,5 alpha-ring A-tetrahydro-reduced derivatives of steroids.
引用
收藏
页码:500 / 505
页数:6
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