Estrogens endocrine disruptors

As an example of suspected endocrine disruptors (EDs), studies of the estrogenic action of bisphenol A (BPA) have been in progress in medical, physiological, and biological fields. In this situation, physicochemical approaches are required to get the structural information of BPA trapped in biomembranes. Most recently, we have determined the site and the orientation of BPA trapped in phospholipid vesicles by NMR, using the HCS rule [47]. In particular, we have succeeded in monitoring the NMR spectral changes of phospholipid vesicles, which are induced by the BPA delivery. 

Endocrine disruptors apparently affect all nuclear receptors. Thus, a notable increment in impotence, alterations of the libido and of oligospermia in workers exposed to pesticides has been described. These alterations are due to the action of some compounds with estrogen-mimetic action and to their interaction with the androgen receptor. Additionally, alterations of thyroid function have been detected in rats exposed to dioxin and other toxic agents,... 

Depending upon the circumstance and desired effects, endocrine-disrupting chemicals can be either good or bad. The endocrine system is a finely balanced system responsible for fertility and many of the feminine and masculine traits we are all familiar with. Endocrine disruptors are used by millions of women in the form of the pill to control fertility. Chemicals in birth control pills subtly manipulate the endocrine system to reduce fertility. Unfortunately, we now know that many chemicals are capable of influencing the endocrine systems. When these chemicals, such as DDT and TCDD, are released into the environment, they reduce the fertility of wildlife. Exposure to endocrine disruptors is linked to decreased fertility in shellfish, fish, birds, and mammals. Endocrine disruptors such as nonylphenol have been shown to feminize male fish, interfering with reproduction. Some studies have also linked exposure to endocrine disruptors to decreases in human male sperm count. Ironically, urinary metabolites of the birth control pill as well as the female hormone estrogen pass through waste treatment plants and are released into the aquatic environment, where even small concentrations cause feminization of male fish. 

Some media outlets trumpeted the 1996 book Our Stolen Future,5 a compilation of mostly unverified observations and speculations, and a paper published in Science that presented startling results purportedly showing that tiny concentrations of some chemicals behaved as endocrine disruptors. Congress rushed legislation that requires billions of dollars to be spent to test chemicals that were regarded as safe except for the alleged estrogenic effects.5... 

At that time (1994-96), I had research support for a project on estrogenic compounds funded by the Chemical Manufacturers Association (CMA) my only official contact with the association was Ann Mason, Director of Scientific and Regulatory Affairs (Chlorine Chemistry Council, CMA), who asked for a yearly report. My opinions on the endocrine disruptor hypothesis have been based on analysis of scientific publications and have been consistent prior to, during, and after the research (not personal) support from the CMA. 

Viglino, L., K. Aboulfadl, M. Prevost, et al. 2008. Analysis of natural and synthetic estrogenic endocrine disruptors in environmental waters using online preconcentration coupled with LC-APPI-MS/MS. Talanta 76 1088-1096. 

The MultiCASE system has been used to identify a common 6-A unit biophore on a range of hormonally active chemicals with estrogenic activity that act as endocrine disruptors. This structural feature is a spacer biophore that is thought to be involved in the molecules binding to the estrogen receptor and is found on the standard estrogenic chemical, 17-beta-estradiol (see Combes, 2000). Other examples of molecules possessing this biophore include 4-hydroxytamoxifen, 2-chloro-4-hydroxybiphenyl, 3,4-dihydroxyfluorene, and 2,2-(fcE-4-hydroxyphenyl-1,1,1 -trichloroethane). 

BPA is considered an endocrine disruptor chemical and, in chronic studies, induces production of vitellogenin in male fathead minnows (P. promelas) at concentrations of 640 and 1280pgl after 43 days and 160pgl after 71 days. Induction of vitellogenin is a process normally occurring only in female fish in response to estrogenic hormones during the reproductive cycle. 

Endocrine disruptors often are structural analogs of endogenous hormones (hormones produced naturally in the host). Hormone analogs may act like the endogenous hormone if the analog-receptor complex in the target cell mimics the function of the hormone-receptor complex. Hydroxy metabolites of both o,p -DDT and methoxychlor bind to estrogen... 

The health effect of endocrine disruptors is further complicated by the fact that an endocrine disrupter or a family of endocrine disruptors may have multiple mechanisms of actions. For example, PCBs may mimic estrogen, prevent binding of thyroid hormone to thyroid binding globulin, and accelerate the metabolism and excretion of several steroid hormones. 

Wastewater from pharmaceutical industries producing these therapeutics may allow introduction of these endocrine disruptors into the ecosystem if proper filtration is not employed. Moreover, the conjugated products excreted in urine and feces from individuals receiving these pharmaceuticals also can be introduced into the wastewater supply. There are few published results regarding bioaccumulation and biotransformation of estrogen-like pharmaceutics released into the ecosystem. 

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