Steroid Hormonal Factors in Populations with Different Risk for Prostate Cancer

A number of studies have compared circulating levels of steroid hormones and other hormonal factors in very high risk African Americans with those in high risk European Americans, lower risk Asian Americans, and very low risk Asians living in Asia or African black men. The details of these studies are summarized in the following paragraphs. Ahluwalia et al. 139 studied African Americans and black Nigerian men that were matched controls in a case control study of prostate cancer. Plasma levels...

Estradiol and Estrone

The mammalian estrogens E2 and estrone (E1), which are interconvertible in the cell by the enzyme 17 -hydroxysteroid dehydrogenase, are human and animal carcinogens 1 . An established animal model is the male Syrian golden hamster, in which carcinogenic estrogens lead to a 100 incidence of kidney tumors. The observation that several potent steroidal estrogens, e.g., 17a-ethinyl-E2 and 2-fluoro-E2, are virtually noncarcinogenic for the hamster kidney 2 is not consistent with the paradigm that...

Tcdd A Putative Antiandrogen

Exposure to aromatic hydrocarbon (Ah) receptor agonists such as TCDD, PCBs, and PCDFs is causally linked to developmental reproductive toxicity in humans, nonhuman primates, rodents, mink, fish, and other wildlife species 171 . Effects are expressed in vertebrates at ppt concentrations. TCDD and other agonists bind a cellular steroid hormone-like receptor, termed the Ah receptor, forming a complex that acts as a transcriptional factor by binding to specific dioxin response elements (DREs) on...

Equine Estrogens

Long-term estrogen replacement therapy of postmenopausal women is associated with a clear risk for endometrial cancer and a possible risk for mammary cancer 18,19 . The most widely prescribed estrogen replacement formulations 4-hydroxy-EQ 4-hydroxy-EQ quinone 4-hydroxy-EQ 4-hydroxy-EQ quinone Fig. 3. Pathways proposed for the metabolic activation of equine estrogens Fig. 3. Pathways proposed for the metabolic activation of equine estrogens in the USA are derived from the urine of pregnant mares...

Antiandrogenic Effects of Phthalate Esters During Development

Recently, concerns about exposure of children to phthalates in toys and other products have resulted in a ban of phthalates in certain toys by the European Union. Although industry has repeatedly assured the safety of these chemicals 161 , most of them, including di-2-ethylhexyl phthalate (DEHP), have never been rigorously examined by the manufacturers for multigenerational effects. The phthalates represent a class of toxicants which alter reproductive development via a mechanism of action that...

Implications of Estrogens in Human Breast Carcinogenesis

Although 67 of breast cancers are manifested during the postmenopausal period, a vast majority, 95 , are initially hormone-dependent 14 . This indicates that estrogens play a crucial role in their development and evolution. It has been established that in situ metabolism of estrogens through aromatase-mediated pathway is correlated with the risk of developing breast cancer 66-69 . A recent finding that expression of estrone sulfatase is inversely correlated with re lapse-free survival of human...

Occupational Exposure to Chlordecone and Dibromochloropropane

Occupational exposure to pesticides and other toxic substances, i.e., chlordecone and dibromochloropropane (DBCP), in the work place have been associated with reduced fertility, lowered sperm counts, and or endocrine alterations in male workers. Workers in Hopewell, Virginia, exposed to high levels of chlordecone, an estrogenic and neurotoxic organochlorine pesticide, displayed obvious signs of intoxication which included severe neurotoxicity and abnormal testicular function 60 . As this cohort...

Diethylstilbestrol

DES is a diphenolic compound synthesized in 1938 53 in the search for an orally effective estrogen. It matches E2 in terms of its affinity to the estrogen receptors and is superior in terms of oral efficacy. DES contributed much to the present concern about carcinogenic effects of estrogens, as it proved to be the culprit of a rare form of vaginal and cervical tumors discovered in 1970 by Herbst et al. 54 and was shown to be a potent carcinogen in several animal models including the Syrian...

Known Effects of Drugs on Human Sexual Differentiation

In humans (and rodents), exposure to hormonally active chemicals during sex differentiation can produce pseudohermaphroditism 21, 35 . In addition, exposure to the androgenic substances, danazol or methyltestosterone, masculinizes human females (i.e., female pseudohermaphroditism). Progestins act both as androgen antagonists, demasculinizing males such that they display ambiguous genitalia with hypospadias 35 , and as androgen agonists, masculinizing females. Laboratory studies demonstrate that...

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...