NEW MODEL FOR EVALUATION OF ENDOCRINE DISRUPTION OF STEROIDOGENESIS BASED ON ADRENOCORTICAL CELL LINE H295R
| Authors | |
|---|---|
| Year of publication | 2005 |
| Type | Article in Proceedings |
| Conference | Chemicals, human and environment |
| MU Faculty or unit | |
| Citation | |
| Field | Environment influence on health |
| Keywords | sterpidogenesis disruption |
| Description | Endocrine disrupting mechanisms of xenobiotics that are released to the environment in large quantities has been very important subject of scientific studies in last years. Main concern was focused on comprehending the process of interaction of xenobiotics with estrogenic receptor which was perceived as the most considerable point of action of endocrine disruptors. As it was shown later, other parts of the steroid signaling pathway are no less important for endocrine disruptors mode of action. Steroidogenesis as a very complex process represents one of them. We used human adrenocorticoid carcinoma cell line H295R which retains ability to synthesize complete set of steroids to develop a model suitable for assessment of the effects of xenobiotics on production of main steroids. Cells were exposed to forskolin (activator of steroidogenesis) and/or tested compound. Levels of main steroids (17-estradiol, testosterone, cortisol, aldosterone, 17-OH-progesterone) were assessed directly in exposition media using commercial Elisa kits. Amounts of steroids obtained were normalized to total protein content in each well. We studied endocrine disrupting effects of several xenobiotics (e.g. POPs: TCDD, B(a)P; pesticides: vinclozolin; pharmaceuticals: metyrapone, spironolactone) on production of steroid hormones. Obtained results show that the effects of the chemicals are compound-specific and that the chemicals can interact with steroidogenesis on multiple levels. For example, incubation of cells with TCDD shows dose dependent increase in production of testosterone and 17b-estradiol while production of androstenedione and 17-OH-progesterone stays unchanged. The developed model shows the effects of xenobiotics on levels of steroids that can be affected by number of factors and thus can bring more complex information than e.g. real time PCR or enzyme activities studies. The procedure is relatively cheap and simple so that this method is suitable for screening purposes. |
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