Occurrence of anabolic agents in plants and their importance

More than 40 plant species have been shown to contain substances that are active in biological assays for estrogenic activity. Such substances may be constitutive metabolic products of a plant, or be formed adaptively in response to environmental factors, such as fungal attack (e.g. coumestrol synthesis in alfalfa infected with Pseudopeziza medicagensis); in other instances estrogens may arise from microbial attack on plant material during storage (e.g. zearalenone formation from corn by Fusarium spp.) Phyto-estrogens may reach man through direct consumption of fresh fruit, vegetables and processed plant products (e.g. administration of olive or cornoil can induce vaginal keratinization in post-menopausal women); or---more relevant to this Symposium---by consumption of carcasses and products from animals fed estrogen-containing forage. Important pasture and forage plants shown to contain phyto-oestrogens include Trifolium subterraneum L, notably the cultivars Dwalganup, Mt. Barker, Yarloop and Marrar, T. pratense (red clover), T. fragiferum L. (strawberry clover), T. alexandrinum (berseem clover), Medicago sativa (alfalfa or lucerne) and Soya hispida (soya beans). A beneficial anabolic action of the estrogens contained in these plants has been implied, but not unequivically established. More attention has been paid to their noxious effects on livestock. On affected T. subterraneum pasture, castrated male sheep showed lactation, squamous metaplasia of the bulbo-urethral glands and urethral stenosis; infertility, variously attributed to suppression of gonadotrophin release and ovulation; faulty ovum transport; premature regression of corpora lutea; irreversible cystic hyperplasia of endometrial glands on prolonged exposure; dystocia and prolapse of the uterus. Sporadic incidence of phyto-estrogen induced infertility in cattle has been reported, attended by ovarian cyst formation. Estrogenic activity in forage plants has been reported from Australia, New Zealand, India, Sweden, Great Britain, Germany, Denmark, Holland, Finland, Egypt and Israel. The clover constituents chiefly incriminated for these effects are glycosides of the isoflavone derivatives genistein and its 4'-methyl ether biochanin-A, daidzein and its 4'-methyl ether formononetin, and pratensein; coumestrol and its 3'- and 4'-methyl ethers account for the estrogenic activity of alfalfa. The isoflavone content of subterranean clover may reach 3 percent of its dry weight, and the coumestrol content of lucerne may exceed 100 mug/g. Coumestrol and genistein compete with 17beta-estradiol for binding sites on the uterine cytoplasmic receptor and induce macromolecular synthesis in the uterus, but fail to induce ovum implantation in ovariectomized, gestagen-maintained rats. Uterotrophic activity of coumestrol and genistein given parenterally to sheep is approximately 10(-3) and 10(-5) times that of stilboestrol, respectively. Biological activity of ingested phytoestrogens is modified by ruminal micro-organisms and hepatic metabolism...