A variety of chemicals have been shown to disrupt female reproductive function throughout the lifespan in laboratory animals and humans (e.g., diethylstilbestrol). These effects include the disruption of normal sexual differentiation, ovarian function (i.e., follicular growth, ovulation, corpus luteum formation and maintenance), fertilization, implantation, and pregnancy. Only a few agents are associated with direct interference with the endocrine reproductive axis. Examples are those with estrogenic activity or the potential to interact with the aryl hydrocarbon (Ah) receptor. Exposure to toxicants during development is of particular concern because many feedback mechanisms functioning in ...view middle of the document...
It has been hypothesized that exposure to organochlorines, some pesticides, and/or polyaromatic hydrocarbons might play a role in the etiology of mammary gland neoplasms via an endocrine disruption pathway, perhaps via an estrogen-mimetic route or alternate estrogen pathways. With respect to the possible role of hormone disruption by chemicals in the occurrence
of breast cancer, there is a lack of sufficient evidence implicating organochlorines in this disease.
ii. Male Reproductive System
Convincing evidence exists in rodents that exposure to chemicals that have estrogenic activity, reduce androgen levels, or otherwise interfere with the action of androgen during development can cause male reproductive system abnormalities that include reduced sperm production capability and reproductive tract abnormalities.
Little is known about the causes of human prostatic cancer, but age, genetics, diet,
endocrine status, and environmental risk factors have been proposed. With respect to the
cause(s) of human prostate cancer, a single retrospective epidemiology study has linked a weak but statistically significant association between acres sprayed with herbicides and prostate cancer deaths. Furthermore, an occupational study of coke oven workers has found an association of coke oven emission with significant excess mortality from cancer of the prostate. Whether herbicide or polyaromatic hydrocarbon exposure contributes to the increasing incidence of human adenocarcinoma of the prostate and whether the mechanism is by way of an endocrine disruption remain to be determined.
iii. Hypothalamus and Pituitary
There are a number of ways that environmental agents may alter neuroendocrine function both during development and in the sexually mature organism. Exposure during development may be of particular concern because many of the feedback functions of the endocrine system are not operational during this period, permanent changes in endocrine function may be induced at levels of exposure to a toxicant that may have no effect in the adult animal, and compounds that may be considered antiestrogenic in the adult (i.e., tamoxifen, dioxin) may act as estrogens in the developing organism. Similarly, exposure to such agents in the adult can modify the feedback of endogenous hormones as well as behavior (i.e., libido, appetite, aggression) of the individual. Because of the complex role that the central nervous system plays in regulating endocrine function, cells within the brain are a potential target for environmental chemicals that have no impact on steroid hormones directly but yet will lead to a disruption of endocrine function.
Numerous environmental agents have been found to alter thyroid hormone levels (e.g., urea derivatives, polyhalogenated biphenyls, and chlorinated dibenzo-p-dioxins). Thyroid hormones are critical to normal growth and development; thus, developmental exposures may have lasting adverse effects.