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首页> 外文期刊>The Journal of Steroid Biochemistry and Molecular Biology >The (+)- and (-)-gossypols potently inhibit both 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase 3 in human and rat testes.
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The (+)- and (-)-gossypols potently inhibit both 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase 3 in human and rat testes.

机译：（+）-和（-）-棉酚有效抑制人和大鼠睾丸中的3β-羟基类固醇脱氢酶和17β-羟基类固醇脱氢酶3。

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Androgen deprivation is commonly used in the treatment of metastatic prostate cancer. The (-)-gossypol enantiomer has been demonstrated as an effective inhibitor of Bcl-2 in the treatment of prostate cancer. However, the mechanism of gossypol as an inhibitor of androgen biosynthesis is not clear. The present study compared (+)- and (-)-gossypols in the inhibition of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-HSD isoform 3 (17beta-HSD3) in human and rat testes. Gossypol enantiomers were more potent inhibitors of rat 3beta-HSD with IC(50)s of approximately 0.2microM compared to 3-5microM in human testes. However, human 17beta-HSD3 was more sensitive to inhibition by gossypol enantiomers, with IC(50)s of 0.36+/-0.09 and 1.13+/-0.12 for (-)- and (+)-gossypols, respectively, compared to 3.43+/-0.46 and 10.93+/-2.27 in rat testes. There were species- and enantiomer-specific differences in the sensitivity of the inhibition of 17beta-HSD3. Gossypol enantiomers competitively inhibited both 3beta-HSD and 17beta-HSD3 by competing for the cofactor binding sites of these enzymes. Gossypol enantiomers, fed orally to rats (20mg/kg), inhibited 3beta-HSD but not 17beta-HSD3. This finding was consistent with the in vitro data, in which rat 3beta-HSD was more sensitive to gossypol inhibition than rat 17beta-HSD3. As the reverse was true for the human enzymes, gossypol might be useful for treating metastatic prostate cancer.
机译：雄激素剥夺通常用于治疗转移性前列腺癌。 （-）-棉酚对映体已被证明是治疗前列腺癌中有效的Bcl-2抑制剂。但是，棉酚作为雄激素生物合成抑制剂的机理尚不清楚。本研究比较了（+）-和（-）-棉酚在人和大鼠睾丸中对3beta-羟基类固醇脱氢酶（3beta-HSD）和17beta-HSD同工型3（17beta-HSD3）的抑制作用。棉酚对映异构体是大鼠3beta-HSD的更有效抑制剂，与人类睾丸中的3-5microM相比，IC（50）约为0.2microM。但是，人17beta-HSD3对棉酚对映体的抑制作用更为敏感，与（3.43）相比，（-）-和（+）-棉酚的IC（50）分别为0.36 +/- 0.09和1.13 +/- 0.12。大鼠睾丸为+/- 0.46和10.93 +/- 2.27。在抑制17beta-HSD3的敏感性上存在物种和对映体特异性差异。棉酚对映异构体通过竞争这些酶的辅因子结合位点竞争性抑制3beta-HSD和17beta-HSD3。口服喂给大鼠的棉酚对映体（20mg / kg）抑制3beta-HSD，但不抑制17beta-HSD3。这一发现与体外数据一致，在体外数据中，大鼠3beta-HSD对棉酚的抑制作用比大鼠17beta-HSD3更敏感。由于人类酶的情况正好相反，棉酚可能对治疗转移性前列腺癌有用。

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