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Endocrine-disrupting agents on healthy human tissues
G Paganetto1, F Campi, K Varani
1Polyolefins G. Natta Research Center, Montell, Ferrara, Italy.
Abstract:
A vast number of substances have been suggested as possibly contributing to perturbation of the endocrine system. Several have been tested with different approaches ranging from yeast expression system of human oestrogenic receptors to human breast cancer cells assays. Surprisingly, no inhibition-binding experiments to steroid receptors on healthy human tissue have been performed so far. Our study provides inhibition binding experiments to oestrogens, progesterone, testosterone and retinoic acid receptors in prostate and uterine human tissue of organochlorine pesticides, phthalate esters, oestrogenic constituents derived from plants and phenol derivates. Affinities of significant extent of phthalates on oestrogenic, progestinic and androgenic receptors have not been detected. As for retinoic acid receptors, mono(2-ethylexyl)phthalate provokes a notable reduction of the binding of the tritiated retinoic acid, phtalic acid ethyl-n-butyl ester and 4-octylphenol show an affinity comparable to that of isoflavonoid genistein, whereas 4-nonylphenol reduces the binding of retinoic acid in prostate.
Insights
This study investigated endocrine-disrupting chemicals
Area of Science:
- Endocrinology
- Toxicology
- Molecular Biology
Background:
- Endocrine system disruption is a growing concern.
- Previous studies used cell-based assays.
- Human tissue binding assays for endocrine disruption were lacking.
Purpose of the Study:
- To investigate the binding affinities of various chemicals to human steroid receptors.
- To assess endocrine-disrupting potential using human tissue samples.
Main Methods:
- Inhibition-binding experiments were conducted.
- Target receptors included oestrogen, progesterone, testosterone, and retinoic acid receptors.
- Human prostate and uterine tissues were utilized.
Main Results:
- Phthalates showed no significant affinity for oestrogen, progesterone, or androgen receptors.
- Mono(2-ethylhexyl)phthalate reduced retinoic acid receptor binding.
- Phthalic acid ethyl-n-butyl ester and 4-octylphenol had retinoic acid binding affinities similar to genistein.
- 4-Nonylphenol reduced retinoic acid binding in prostate tissue.
Conclusions:
- Certain phthalates and phenols interact with retinoic acid receptors.
- This interaction may contribute to endocrine disruption.
- Human tissue binding assays are crucial for assessing chemical safety.