SCREENING AND BIOLOGICAL CHARACTERIZATION OF SOME NATURAL/SYNTHETIC ENDOCRINE DISRUPTORS

Abstract

Endocrine system and nervous system are two major modes of communication that coordinate and control different body functions. While the dynamics of nervous system is maintained by conduction of electrical impulses through the complex circuits, the messengers of the endocrine system are hormones that are synthesized and excreted at very low quantities from specialized glands and transported to the target organ(s) via the bloodstream. A tuned functioning of endocrine orchestra is necessary for sustained maintenance of different pivotal functions in human or animal body like reproduction and development, growth and maturation, energy production, electrolyte balance etc. However, increasing scientific evidences depict the existence of a newly defined category of environmental contaminants which may have diverse chemical structures and can alter the normal functioning of the endocrine and reproductive systems (Cargouet et al., 2004). These chemicals mimic/ inhibit the actions of endogenous hormones or modulate the synthesis of latter and have been named as 'endocrine disrupting chemicals' (EDC) (Sonnennschein and Soto, 1998). In this way EDC may interfere with usual hormonally regulated biological processes and thus, may adversely affect the development and reproductive function in wildlife, experimental animals, and humans (Satoh et al., 2001). In general EDC have been defined as- "An exogenous agent that interferes with the synthesis, storage/release, transport, metabolism, binding, action or elimination of natural blood-borne hormones responsible for the regulation ofhomeostasis and ofdevelopmental processes". Depending on the mode of action, EDC can be broadly categorized as androgenic or antiandrogenic chemicals, causing disturbances in production of androgens or estrogenic/ anti-estrogenic chemicals, when they affect the production ofestrogens. EDC may enter into the body of animals/humans through the diet, contaminated water or occupational exposure and may lead to the generation ofan agonistic or antagonistic effect (Kumar et al., 2008a, Kumar et al., 2008b). Once inside the physiological system the EDC may exert their effect by acting at one or more of the following steps: (i) through arylhydrocarbon receptor (AhR) (Indarto and Izawa, 2001) (ii) direct binding ofthese chemicals to steroid receptors, steroidogenic enzymes and proteins associated with steroidogenesis (like StAR protein) (Walsh et al, 2000, Sanderson and Vanden Berg, 2003; Rice et al, 2006), and (iii) increasing the stability oftranscripts and transcriptional rate of the promoter of steroidogenic enzymes (Lin et al, 2006; Lyssimachou et al, 2006). An increasing body of evidences reveals association between various therapeutic/environmental compounds that act as EDC and many sex hormone-sensitive disease/disorders (Colborn and Clement, 1992; Satoh et al., 2001; Sone et al., 2005; Guillette, 2006; Massart et al., 2006; Chen et al., 2007). A probable link have been proposed between exposure to EDC and production ofa number ofdiseases like reduced fecundity, abnormal fetal development, delayed onset of puberty, cryptorchadism, abnormal lactation, testicular dysfunction and even various types of cancers (Sharpe and Irvine, 2004; Roy et al, 2005; Buck et al., 2006; Darbre, 2006; Guillette, 2006; Maffini et al, 2006). In the past decade, the utilization of many chemicals (including pesticides and persistent organic pollutants) has declined worldwide diminishing the chances of human/ animal exposure to them. However, the chemicals having endocrine disrupting (ED) potential are being used directly or indirectly for diverse purposes in different sectors of life ranging from the simple household activities like detergents, cosmetics and toilet articles to specialized applications viz. pharmaceuticals, insecticides and pesticides. Many of these chemicals are being released into the environment from various sources (household activities, industrial manufacturing, agricultural applications etc) without prior evaluation of their endocrine activity at the molecular levels. Once these chemicals reach the environment they may enter into the food chain and finally reaching the animal/human systems (Roy et al., 2005). Although the carcinogenic potential of these compounds are evaluated by routine mutagenicity testing or simple biophysical tests but the concentrations necessary to disrupt endocrine regulation may be lower than required to act as a carcinogen. Life long intake of even very low levels of these compounds may disturb the delicate hormone balance and compromise the reproductive fitness and health of many species (Ralph et al, 2003). All this has led to the widespread occurrence of EDC in food chain and different strata of environment in many forms like persistent organic pollutants (POPs) such as the insecticide dichlorodiphenyl-trichloroethane (DDT) and its metabolites, the industrial by-product dioxins, the industrial compounds polychlorinated biphenyls (PCB), several agrochemicals, pesticides and biocides (e.g. chlorinated insecticides, organotins, imidazoles, triazoles, etc.) and other industrial compounds (several phenol compounds such as bisphenol A) (Mantovani et al., 1999). According to one ofthe enviornmetal scientist (Trivedi, 2007)- "Today and every day, you can expect to be exposed to some 75,000 artificial chemicals. All day long you will be breathing them in, absorbing them through your skin and swallowing them in yourfood. Throughout the night they will seep out of carpets, pillows and curtains, and drift into your lungs. Living in this chemical soup is an inescapable side effect of 21st-century living. The question is: is it doing us any harm?"