Endocrine Compounds and Health Effects

What do these Endocrine Disrupting Compounds and Estrogen Mimicking Compounds do to us ?

Understanding how endocrine-disrupting compounds (EDCs) cause health risks has troubled researchers and environmentalists for decades. Even after the explosive generation of information from the genome project and now the proteome project, we are still in confusion as to how these compounds can do some much harm. In order to understand endocrine-disrupting compounds (EDCs), it is of prime importance to understand human endocrine physiology before we can fully understand these compounds.

Estrogen Effects: Mechanisms and Alterations of Human Physiology

Estrogen action affects bone, skin, the brain and cardiovascular system, as well as other peripheral tissues in both men and women. Similarly, androgens are crucial directors of growth for pubertal growth during adolescence in both boys and girls, as well as in the formation and maintenance of the male reproductive system and for spermatogenesis. endocrine-disrupting compounds (EDCs) can either mimic estrogen and/or androgen, thereby acting as agonists hyperstimulating the given steroids effects in tissue by over-activating the steroid receptor through stronger conformational changes. In contrast, endocrine-disrupting compounds (EDCs) can also act as inhibitors, antagonists, blocking the steroids effects by simply binding to the receptor and blocking the entrance of other molecules. Bisphenol A and DES, as well as other anthropogenic chemicals, have been known since the 1930’s to have an uterotrophic estrogenic effect (IPCS, 2002; Yang et al, 2006). DDE and certain PCDs are known to have antiandrogenic alterations that have been postulated to cause demasculinization and feminization of male offspring, with the opposite effects seen in female offspring (Colborn et al, 1996).

Steroid Receptors, Endocrine-Disrupting Compounds (EDCs) and Breast Cancer

In addition to directly affecting the steroid receptor, endocrine-disrupting compounds (EDCs) can also affect the last step of estrogen synthesis by blocking the enzyme involved, aromatase, which allows the liver to subsequently clear circulating estrogen more easily (Brodie et al, 1999). Endocrine-disrupting compounds (EDCs) can also interact with circulating steroid binding proteins, which carry steroids throughout the circulation to distant organs and cells, as steroids are lipophilic and hydrophobic and therefore need serum transporters, such as sex hormone binding globulin (SHBG) (Kaminuma et al, 2000). Endocrine-disrupting compounds (EDCs) can bind to these molecules and take up space and/or displace other steroid molecules already bound, leading to variations in steroid blood levels. The most serious effects of endocrine-disrupting compounds (EDCs) however, are the ability of some to modify pre-existing steroids and create resistant forms that the body is unable to clear effectively. PCBs and PAHs, which are both products of combustion, are strong inhibitors of sulphotransferase-1, which is an enzyme, found in the liver that sulphates estrogen precursors, so they may become hydrophilic and lipophobic in order to allow them to enter the urine or stool to be excreted. Such suppression prolongs estrogen action and estrogen levels in the body, a change that has recently been linked to breast cancer (Sharpe et al, 2004; Yang et al, 2006).

Endocrine-Disrupting Compounds (EDCs) Future Health Threat

With such a diversity of actions and intrusion onto the human endocrine system, it is not a surprise that endocrine-disrupting compounds (EDCs) have become implicated in numerous disorders and syndromes, of which, similar to many endocrine-disrupting compounds (EDCs), are now on the rise and never did they exist prior to the 19th century. Moreover, endocrine-disrupting compounds (EDCs) pose a serious threat to the future of the human population.

 

References:

IPCS. 2002. Global assessment of state-the-science of endocrine disruptors, international programme of chemical safety. World Health Organization, Geneva: Switzerland.

Yang M, Park MS, and Lee HS. 2006. Endocrine Disrupting Chemicals: Human Exposure and Health Risks. J. Environmental Science and Health Part C. 24: 183-224.

Colborn T., Dumandski D., and Myers J.P. 1996. Our Stolen Future. New York.

Brodie A., Dowsett M., Lonning P., and Miller W. 1999. Aromatase and its inhibitors: new biology and clinical perspectives. Endocrine-Related Cancer. 6(2):127-130.

Kaminuma T., Nakano T., Nakata K., and Takai-Igarashi T. 2000. Modeling of signalling pathways for endocrine disruptors. BioSystems. 55:23-31

Yang M, Park MS, and Lee HS. 2006. Endocrine Disrupting Chemicals: Human Exposure and Health Risks. J. Environmental Science and Health Part C. 24: 183-224.