Department of Dietetics, Nutrition and Biological Sciences, Queen Margaret University Edinburgh, Queen Margaret University Drive, Musselburgh, East Lothian EH21 6UU, UK.
Mol Cell Endocrinol. 2011 Apr 10;336(1-2):102-9. doi: 10.1016/j.mce.2010.12.011. Epub 2010 Dec 22.
The mineralocorticoid effects of liquorice are mediated by the inhibitory effects of one of its active components glycyrrhetinic acid on 11β-hydroxysteroid dehydrogenase type 2. However, liquorice is reputed to have many medicinal properties and also contains a number of other potentially biologically active compounds. Here we have investigated the wider effects of oral liquorice on steroidogenesis focussing particularly on possible inhibitory effects of glycyrrhetinic acid on adrenal sulfotransferase activity. Salivary steroids were profiled by ELISA in groups of normal male and female volunteers after consuming either liquorice-containing or non-liquorice-containing confectionary for one week. Cortisol and cortisone levels reflected expected inhibition of 11β-hydroxysteroid dehydrogenase type 2 by glycyrrhetinic acid. Salivary aldosterone was decreased but deoxycorticosterone, dehydroepiandrosterone and testosterone were increased. To assess whether glycyrrhetinic acid directly affected steroidogenesis, free and conjugated steroids were measured in incubates of adrenocortical H295 cells, firstly, in the presence or absence of forskolin and secondly, with radiolabeled deoxycorticosterone or dehydroepiandrosterone. Glycyrrhetinic acid inhibited cortisone and enhanced cortisol synthesis consistent with 11β-hydroxysteroid dehydrogenase type 2 inhibition. Basal and forskolin-stimulated syntheses of deoxycorticosterone and dehydroepiandrosterone conjugates were also inhibited in a dose-dependent manner; glycyrrhetinic acid inhibited the conjugation of deoxycorticosterone and dehydroepiandrosterone with IC50 values of 7 μM. Inhibition of deoxycorticosterone and dehydroepiandrosterone conjugation was apparent within 4 h of starting glycyrrhetinic acid treatment and was not associated with changes in the expression of SULT 2A1 mRNA. SULT2A1 encodes the enzyme sulfotransferase 2A1 which is responsible for the sulfonation of deoxycorticosterone and dehydroepiandrosterone as well as pregnenolone and 17-hydroxypregnenolone in human adrenal glands. We suggest that the glycyrrhetinic acid constituent of liquorice increases circulating and thereby, salivary levels of unconjugated deoxycorticosterone and dehydroepiandrosterone by inhibiting their conjugation at source within the adrenal cortex. This effect may contribute to the mineralocorticoid actions of glycyrrhetinic acid and gives substance to claims that liquorice also has androgenic properties.
甘草的盐皮质激素作用是通过其活性成分之一甘草酸对 11β-羟甾脱氢酶 2 型的抑制作用介导的。然而，甘草据称具有许多药用特性，并且还含有许多其他潜在的生物活性化合物。在这里，我们研究了甘草的口服对类固醇生成的更广泛影响，特别关注甘草酸对肾上腺硫酸转移酶活性的可能抑制作用。在一周内，分别给正常男性和女性志愿者食用含甘草或不含甘草的糖果后，通过 ELISA 对唾液类固醇进行了分析。皮质醇和皮质酮水平反映了甘草酸对 11β-羟甾脱氢酶 2 型的预期抑制作用。唾液醛固酮减少，但脱氧皮质酮、脱氢表雄酮和睾酮增加。为了评估甘草酸是否直接影响类固醇生成，首先在有无 forskolin 的情况下，其次在用放射性标记的脱氧皮质酮或脱氢表雄酮孵育的肾上腺 H295 细胞中测量游离和共轭类固醇。甘草酸抑制皮质酮并增强皮质醇合成，与 11β-羟甾脱氢酶 2 型抑制一致。脱氧皮质酮和脱氢表雄酮缀合物的基础和 forskolin 刺激合成也呈剂量依赖性抑制；甘草酸抑制脱氧皮质酮和脱氢表雄酮与 IC50 值为 7 μM 的缀合。甘草酸处理开始后 4 小时内即可观察到脱氧皮质酮和脱氢表雄酮缀合的抑制，并且与 SULT2A1 mRNA 表达的变化无关。SULT2A1 编码负责人类肾上腺中脱氧皮质酮和脱氢表雄酮以及孕烯醇酮和 17-羟孕烯醇酮磺化的酶硫酸转移酶 2A1。我们认为，甘草中的甘草酸成分通过抑制肾上腺皮质中源头上的缀合，增加了未结合的脱氧皮质酮和脱氢表雄酮的循环和唾液水平。这种作用可能有助于甘草酸的盐皮质激素作用，并使甘草也具有雄激素特性的说法有了依据。
