Potential Effects of Toxicants on Sex Ratio in Humans and Animals

The effects of exposure to endocrine disruptors during sex differentiation are of special concern for a number of reasons this process is very sensitive to the effects of relatively low doses of endocrine disruptors, the effects are irreversible, i. e., the system is imprinted by the initial hormonal environment, functional alterations of the sex differentiation are often not apparent until after puberty or even later in life, and the abnormalities, which include malformations and infertility,...

And Environmental Androgens and Antiandrogens

Earl Gray Jr.Christy Lambright2, Louise ParksRochelle W. Tyl2, Edward F. Orlando3, Louis J. Guillette Jr.3, Cynthia J. Wolf1, John C. Seely4, Tsai-Yin Chang2, Vickie Wilson5, Andrew Hotchkiss5, Joseph S. Ostby1 1 Endocrinology Branch, Reproductive Toxicology Division, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA E-mail emgray mindspring.com, gray.earl epa.gov 2 Research Triangle Institute, Research Triangle Park, North Carolina, USA 3 University of...

Metabolism of Dietary Estrogens

The major isoflavones, genistein and daidzein, commonly exist as inactive glycosides 11 . They are derived from precursors, biochanin A and formononetin, which are converted to genistein and daidzein, respectively, after breakdown by intestinal glucosidases 15 . Daidzein is further metabolized to the mammalian isoflavone metabolites, equol and O-demethylangiolensin (O-Dma) (Fig. 1) 15, 16 . Absorbed phytoestrogen metabolites undergo enterohepatic circulation and may be excreted in the bile as...

Importance of Non Monotonic InvertedU Dose Response Curves

The issue of the sensitivity of fetuses to extremely small differences in circulating gonadal steroid levels is critical with regard to the very high doses traditionally used in toxicological studies. In the following two sections we will discuss data that demonstrate opposing effects of high and low doses of natural hormones, vitamins, and EDCs. These results suggest that it is inappropriate to assume that one can predict effects of low doses of EDCs from results obtained at high doses. The...

Biological Potencies of Dietary Estrogens

Phytoestrogen are of biological interest because they exhibit both in vivo and in vitro weak estrogenic and anti-estrogenic actions through their binding to ERs 68 . The dual action of phytoestrogens as agonists and antagonists has resulted in a general confusion in the literature regarding the role these compounds may play in disease progression and or protection. In common with many other weak estrogens, isoflavones have been shown to be anti-estrogens in model systems, competing for E2 at...

Chemical Carcinogens Combined with Hormonal Stimulation of Cell Proliferation

Induction of prostatic adenocarcinomas by chemical carcinogens is rare. Only two organic chemical carcinogens, i.e., N-nitroso-bis-(oxopropyl)amine (BOP) and 3,2'-dimethyl-4-aminobiphenyl (DMAB), cause prostate adenocarcinomas upon systemic administration, without any additional concomitant or subsequent treatment 217, 218 . Direct application of chemical carcinogens to prostate tissue in experimental animals produces sarcomas or squamous cell carcinomas (see 5,219 ). Hormonal stimulation of...

Known Effects of Plant and Fungal Estrogens in Animals and Humans

The phytoestrogens and fungal mycotoxins provide some of the most conclusive data demonstrating that environmental estrogens are toxic to mammalian reproductive function under natural conditions. Naturally occurring compounds with estrogenic and other endocrine activities are widespread in nature. Farnsworth et al. 46 listed over 400 species of plants that contain potentially estrogenic isoflavonoids or coumestans or were suspected of being estro- genic based on biological grounds. Plants...

References

Colborn T, Clement C (1992) Chemically-induced alterations in sexual and functional development the wildlife human connection. Princeton Scientific Publishing, Princeton 2. Alleva E, Brock J, Brouwer A, Colborn T, Fossi MC, Gray E, Guillette L, Hauser P, Leatherland J, MacLusky N, Mutti A, Palanza P, Parmigiani S, Porterfield S, Santti R, Stein SA, vom Saal F, Weiss B (1998) Toxicol Ind Health 14 1 3. Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, Guilette LJ Jr, Jegou B,...

Beneficial and Adverse Effects of Dietary Estrogens on the Human Endocrine System Clinical and Epidemiological Data

Stanford University School of Medicine, 300 Pasteur Drive, Room S-308, Stanford, E-mail doris.tham forsythe.stanford.edu Dietary estrogens, also known as phytoestrogens, represent a family of plant compounds which are of biological interest because they exhibit both in vivo and in vitro weak estrogenic and anti-estrogenic properties. Phytoestrogens appear to exert their physiological effects through a variety of possible mechanisms, such as their ability to bind to estrogen receptors and their...