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Isoflavonoids and lignans, constituents of many plant foods, have been proposed as protective agents in those populations with a low incidence of hormone-dependent cancers. They may act by their inhibition of the metabolism of growth-promoting steroid hormones. This report describes the inhibition of 5-reductase and 17β-hydroxysteroid dehydrogenase by six isoflavonoids and two lignans in human genital skin fibroblast monolayers and homogenates, and in benign prostatic hyperplasia tissue homogenates. In genital skin fibroblasts, genistein, biochanin A and equol were the most potent inhibitors of 5-reductase activity, each resulting in greater than 80% inhibition at a concentration of 100 µm. The IC₅₀ values for genistein and a seven-compound mixture were approximately 35 µm and 20 µm (2·9 µm of each compound) respectively. Of the lignans, enterolactone was the most potent inhibitor. Inhibition by biochanin A was shown to be reversible. When genital skin fibroblast homogenates were used, biochanin A was found to inhibit 5-reductase isozymes 1 and 2 to differing extents (30% and 75% respectively). Genistein was shown to inhibit 5-reductase 2 in a non-competitive nature (V^max and K^m values without and with inhibitor were 30 and 20 pmol/mg protein per h and 177 and 170 nm respectively). All of the compounds tested inhibited 17β-hydroxysteroid dehydrogenase activity in genital skin fibroblast monolayers. When prostate tissue homogenates were used, the compounds tested were better inhibitors of 5-reductase 1 than 2. It is possible that a life-long dietary exposure to these lignans and isoflavonoids may have a significant influence on the development of hormone-dependent tumours.

Journal of Endocrinology (1995) 147, 295–302

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