Evaluation of estrogenic activity of parabens and their chlorinated derivatives by using the yeast two‐hybrid assay and the enzyme‐linked immunosorbent assay

Terasaki, Masanori; Kamata, Ryo; Shiraishi, Fujio; Makino, Mitsunori

doi:10.1897/08-225.1

Cited by 48 publications

(26 citation statements)

References 33 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Also parabens, which are similar in size and shape to MC, were shown to exhibit estrogenic activity (66). Further- more, MC fits well to the binding pocket of ER (Fig.…”

Section: Discussionmentioning

confidence: 63%

Dual Activities of Odorants on Olfactory and Nuclear Hormone Receptors

Pick

Etter

Baud

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

We have screened an odorant compound library and discovered molecules acting as chemical signals that specifically activate both G-protein-coupled olfactory receptors (ORs) on the cell surface of olfactory sensory neurons and the human nuclear estrogen receptor ␣ (ER) involved in transcriptional regulation of cellular differentiation and proliferation in a wide variety of tissues. Hence, these apparent dual active odorants induce distinct signal transduction pathways at different subcellular localizations, which affect both neuronal signaling, resulting in odor perception, and the ER-dependent transcriptional control of specific genes. We demonstrate these effects using fluorescence-based in vitro and cellular assays. Among these odorants, we have identified synthetic sandalwood compounds, an important class of molecules used in the fragrance industry. For one estrogenic odorant we have also identified the cognate OR. This prompted us to compare basic molecular recognition principles of odorants on the two structurally and apparent functionally non-related receptors using computational modeling in combination with functional assays. Faced with the increasing evidence that ORs may perform chemosensory functions in a number of tissues outside of the nasal olfactory epithelium, the unraveling of these molecular ligand-receptor interaction principles is of critical importance. In addition the evidence that certain olfactory sensory neurons naturally co-express ORs and ERs may provide a direct functional link between the olfactory and hormonal systems in humans. Our results are therefore useful for defining the structural and functional characteristics of ER-specific odorants and the role of odorant molecules in cellular processes other than olfaction.Our nose detects a large variety of odorant signals relying on about 350 different predicted G-protein-coupled olfactory receptors (ORs) 3 with a conserved seven-transmembrane helical structure (1-3). By binding odorant molecules ORs modulate the conversion of chemical into electrical neuronal signals that are finally decoded in higher brain regions to trigger emotional and behavioral responses (4 -6). Odorants are generally small, hydrophobic organic molecules with highly variable chemical structures and properties (7). They easily pass cell membranes, and, due to their enormous chemical diversity, some of them might, apart from their "conventional" role in olfaction, trigger also yet unknown cellular processes. The role of specific ORs in sperm chemotaxis has been documented (8,9), and the widespread ectopic expression of OR genes in a large number of non-olfactory human tissues implicates additional, unproven functions of ORs in embryonic development and cell-cell recognition (10), and proliferation rates in prostate cancer cells (11). Recent findings indicate that ORs might also have chemosensory functions in kidney (12). Although most present efforts concentrate on matching odorants with their cognate ORs to define their molecular receptive ranges and receptor fu...

show abstract

“…Also parabens, which are similar in size and shape to MC, were shown to exhibit estrogenic activity (66). Further- more, MC fits well to the binding pocket of ER (Fig.…”

Section: Discussionmentioning

confidence: 63%

Dual Activities of Odorants on Olfactory and Nuclear Hormone Receptors

Pick

Etter

Baud

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Interestingly, significant positive correlations were observed between the concentrations of 3,5-2Cl-MeP and MeP (R = 0.350, p b 0.01), as well as 3,5-2Cl-EtP and EtP (R = 0.321, p b 0.01) in these samples (Table S4). These results suggest that these chlorinated derivatives were originated when personal care products containing parabens reached chlorinated water, and then released into aquatic environments (Albero et al, 2012;Terasaki et al, 2009a).…”

Section: Concentrations Of Parabens Chlorinated Parabens and Phba Imentioning

confidence: 88%

Spatial distribution, temporal variation and risks of parabens and their chlorinated derivatives in urban surface water in Beijing, China

Gao

Shi

et al. 2016

Science of The Total Environment

View full text Add to dashboard Cite

“…In vitro studies suggest that parabens can interfere with steroidogenesis (PB-Me, -Et, -Pr, -Bu) and expression of receptor proteins (PB-Bu) (Okubo et al, 2001;Taxvig et al, 2008). PB-Bu and -Pr but not -Me or -Et showed estrogenic properties in a yeast two-hybrid bioassay (Morohoshi et al, 2005;Terasaki et al, 2009). PB-Me was also able to increase the expression of a stably integrated estrogen responsive reporter gene (ERE-CAT) in MCF-7 cells at 1EÀ4 M (Pugazhendhi et al, 2005).…”

Section: Preservatives and Antimicrobialsmentioning

confidence: 99%