Endocrine Disruptor—A threat to the animal world

Various types of naturally occurring and artificially made chemicals cause disruption of endocrine processes among animals. They mimic biochemically with hormones and interfere with the normal signaling and activity of the endocrine system, causing enormous changes at the cellular level of animals from lower to higher organisms, including human being. These modified regulations of cellular activities as a result of endocrine disruptors have severe implications at the organismal level. Types and adverse effects of these natural and synthetic agents, especially estrogenic compounds causing biological threats have been discussed in details in this review.

Physiologically Relevant Estrogen Receptor Alpha Pathway Reporters for Single-Cell Imaging-Based Carcinogenic Hazard Assessment of Estrogenic Compounds

Estrogen receptor alpha (ERα) belongs to the nuclear hormone receptor family of ligand-inducible transcription factors and regulates gene networks in biological processes such as cell growth and proliferation. Disruption of these networks by chemical compounds with estrogenic activity can result in adverse outcomes such as unscheduled cell proliferation, ultimately culminating in tumor formation. To distinguish disruptive activation from normal physiological responses, it is essential to quantify relationships between different key events leading to a particular adverse outcome. For this purpose, we established fluorescent protein MCF7 reporter cell lines for ERα-induced proliferation by bacterial artificial chromosome-based tagging of 3 ERα target genes: GREB1, PGR, and TFF1. These target genes are inducible by the non-genotoxic carcinogen and ERα agonist 17β-estradiol in an ERα-dependent manner and are essential for ERα-dependent cell-cycle progression and proliferation. The 3 GFP reporter cell lines were characterized in detail and showed different activation dynamics upon exposure to 17β-estradiol. In addition, they demonstrated specific activation in response to other established reference estrogenic compounds of different potencies, with similar sensitivities as validated OECD test methods. This study shows that these fluorescent reporter cell lines can be used to monitor the spatial and temporal dynamics of ERα pathway activation at the single-cell level for more mechanistic insight, thereby allowing a detailed assessment of the potential carcinogenic activity of estrogenic compounds in humans.

Natural and Synthetic Estrogens Regulate Human Health

Estrogen are very important chemical compounds very essential for our body functions. The cholesterol, what we eat through food, gets converted by the action of various enzymes. Scientists have synthesized estrogenic molecules in the laboratory and used them for oral contraceptives and other therapeutic purposes. Environmental estrogenic molecules (xenestrogen) played havocs in human life. Plants also make estrogenic substances (phytoestrogen); they are very useful for mankind. All steroid hormones, including estrogen are synthesized from cholesterol through a common precursor steroid, pregnenolone which is formed by the enzymatic cleavage of a 6-carbon side-chain of the 27-carbon cholesterol molecule. Cholesterol is a starting substance of group of estrogenic compounds [1]. On the other hand, synthetic estrogen are compounds obtained by chemical synthesis that possess estrogenic activity [2]. In addition to these estrogenic compounds there are some estrogenic action mimicking compounds known as xenestrogen and phytoestrogen (Figure 1).