• Journal of Environmental Health Sciences
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• v.42 no.3
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• pp.169-188
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• 2016

Objectives: Although information on the toxicity of phthalate diesters is readily available, little is known about phthalate alternatives. The present article provides a summary of available information on the toxicity of phthalate diesters and their alternatives, with a special focus on estrogenicity and androgenicity. Methods: We collected a battery of in vitro and in vivo assay data from the literature to assess the estrogenicity/anti-estrogenicity and androgenicity/anti-androgenicity of 15 phthalate diesters and 21 phthalate alternatives. Results: A number of in vitro studies show that certain phthalate diesters can bind to estrogen receptors and have a weak estrogenic potential. However, this potential was not seen in in vivo studies. Phthalate diesters produced anti-androgenic effects in animals by reducing testosterone production. Among them, di-(2-ethyl-hexyl) phthalate (DEHP) was the most potent. While almost all phthalate alternatives have a lower toxic potential than does DEHP, evidence of reproductive toxicity and estrogenic potential were found in several substances. Conclusion: Significant data gaps exist for phthalate alternatives regarding reproductive endocrine disruption, requiring further investigation.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.166-166
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• 2002

The response of environmental pollutants can be detected bioanalytically focusing on the source and matrices of concern. Cell culture bioassays are rapid and inexpensive, and thus have great potential for determination of environmental pollution. We have examined the estrogenic and dioxin-like activites of industrial wastewater using E-screen assay and EROD microbioassay. Influent and effluent wastewater were collected from four different industrial wastewater treatment plants, such as cosmetics, paints, textile producing and metal coating plant, and extracted using solid-phase extraction with Oasis＠HLB plus cartridge. Pollutants adsorbed to the cartridge were eluted with MTBE. MCF-7 cells were treated with extracts showed various estrogenic potential. The textile wastewater showed strong estrogenic activity and the others showed weak estrogenic activity, No effect was observed in the wastewater from paints producing plant. All extracts showed CYPIA inducing effects, indicating these samples contain dioxin-like chemicals. Bioanalytical results of effluents compared with influents could give us information about the incomplete wastewater treatment and biological potency caused by pollutants. [Supported by a Grant from the Korea Science and Engineering Foundation]

• The Korea Journal of Herbology
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• v.37 no.5
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• pp.1-8
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• 2022

Objectives : This study aimed to investigate the synergistic effect of combining Cynanchi Wilfordii Radix extract with Humuli Lupuli Flos extract on estrogenic and anti-osteoclastogenic activity. Methods : Estrogenic effect of a mixture of Cynanchi Wilfordii Radix extract and Humuli Lupuli Flos extract (CWHL), Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin (an active ingredient of Cynanchi wilfordii Radix extract) and 8-prenylnaringenin (an active ingredient of Humuli Lupuli Flos extract) were examined by proliferation E-screen assay and expression of estrogen inducible gene, pS2 via Real Time-PCR (RT-PCR) in MCF-7 estrogen responsive cells. And their estrogenic activities were investigated how to modulate Estrogen receptor 𝛽 by binding affinity assay. Inhibitory effect of CWHL, Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin and 8-prenylnaringenin on RANKL-induced osteoclast differentiation were tested by TRAP (Tartrate-resistant acid phosphatase) staining in osteoclastogenic RAW 264.7 cells. Results : CWHL, Humuli Lupuli Flos extract and 8-prenylnaringenin accelerated the proliferation of MCF-7 and the expression of pS2 in MCF-7. CWHL, Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin and 8-prenylnaringenin bind to estrogen receptor 𝛽. CWHL, Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin and 8-prenylnaringenin inhibited RANKL-induced osteoclastogenesis in osteoclastogenic RAW 264.7. CWHL is more effective for all markers than Cynanchi Wilfordii Radix extract or Humuli Lupuli Flos extract alone. Conclusions : CWHL may a potential therapeutic agent for menopause and osteoporosis as a natural food resource. CWHL as a natural food source has therapeutic potential in cases of menopause and osteoporosis.

• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.106-113
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• 2006

Phthalate analogues are a plasticizer and solvent used in industry. Phthalates were classified in the category of "suspected" endocrine disruptors. The purpose of our study was to screen and elucidate the endocrine disrupting activity of seven phthalate analogues. E-screen assay was performed in MCF-7 human breast cancer cells with seven phthalate analogues. In this cell proliferation assay, benzyl butyl phthalate (BBP) and dibutyl phthalate (DBP) showed high estrogenic activity. Their relative proliferation efficiencies (RPE) were 109 and 106%, respectively. In vitro estrogen receptor (ER) binding assay, BBP, di-n-octyl phthalate (DOP) and dinonyl phthalate (DNP) showed weak relative binding affinity (RBA: 0.02%) compared to $17{\beta}-estradiol\;(E2)$ (RBA: 100%). In uterotrophic assay, E2 produced a significant increase, whereas four tested phthalate analogues had potential estrogenic effects in vitro did not increased in uterus weight in immature rats. From these results, we demonstrated that phthalate analogues exhibit weak estrogenic activity in vitro assays at high concentrations. Although phthalates induced an increase in MCF-7 cell proliferation by an estrogenic effect, they could not induce a uterus weight increase in vivo. From these, we may suggest that these phthalate analogues are easily metabolized to inactive forms in vivo. Further investigation in other in vitro and in vivo experimental systems might be required.

• Korean Journal of Pharmacognosy
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• v.52 no.2
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• pp.118-125
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• 2021

Leguminosae plants are known for its phytoestrogen constituents which play a major role in the prevention of osteoporosis, cancer and heart disease. In this study, the estrogenic activity of 158 samples from 58 species, 3 subspecies and 10 varieties of Leguminosae plants growing in Korea was evaluated. An estrogen, 17β-estradiol was used as a reference compound, and the potency of each sample was expressed in relative efficacy (%) compared to that of the reference by a reporter gene assay using MCF-7 cells. As results, the estrogenic activity of methanolic extracts of Phaseolus vulgaris var. humilis, Sophora flavescens, Lespedeza × robusta, Indigofera pseudotinctoria, Maackia amurensis, Glycine soja, Wisteria floribunda, Robinia pseudoacacia, Astragalus sinicus, Pueraria lobata, Lespedeza maximowiczii var. tomentella, Trifolium repens and Crotalaria sessiliflora showed similar to or higher at 100 ㎍/ml than the positive control at 10 nM. These findings can be a potential evidence for developing estrogen alternatives resolving various types of menopause symptoms with information on proper harvest season and usage plant part. To the best of our knowledge, the estrogenic activity of Lespedeza × robusta, Indigofera pseudotinctoria, Wisteria floribunda, Robinia pseudoacacia and Lespedeza maximowiczii var. tomentella is reported for the first time in this study.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.166-166
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• 2002

In the present study, estrogenic or antiestrogenic activity of cypermethrin, a pyrethroid insecticide was investigated. We used immature rat uterotrophic assay, estrogen-responsive calbindin-D9k (CaBP-9k) gene expression assay and luciferase reporter gene assay for measure of estrogenic potential of cypermethrin.(omitted)

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.354-362
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• 2006

Dietary flavonoids have attracted a great deal of attention as agents for preventing estrogen-related diseases, such as postmenopausal symptoms, and for reducing the risk of estrogen-dependent cancer. Kaempferol is one of the most commonly found dietary phytoestrogen. The aim of this study was to investigate the estrogenic and/or antiestrogenic effect of kaempferol, which can confirm its potency as a preventive agent against estrogen-related diseases. Kaempferol has both estrogenic and antiestrogenic activity, which are biphasic response on estrogen receptor. The estrogenic activity of kaempferol induced via ER-mediated pathway depending on $E_2$ concentration $(\leq\;10^{-12}M)$. Kaempferol $(10^{-5}\;M)$ also caused antiproliferative effect on MCF-7 cell in the presence of $E_2\;(10^{-11}\;M)$ and restored to the addition of excess $E_2\;(10^{-7}\;M)$, which confirms that antiproliferation of kaempferol was induced via ER-dependent pathway. However, at $10^{-4}\;M$, concentration higher than the concentrations at which the estrogenic effects of kaempferol are detected $(10^{-5}\;M)$, kaempferol induced strong antiproliferative effect, but were unaffected by the addition of excess $E_2\;(10^{-7}\;M)$ indicating that kaempferol exerts antiproliferation via ER-independent pathway. In particular, kaempferol blocked the focus formation induced by $E_2$, which confirms that kaempferol might inhibit the malignant transformation caused by estrogens. Therefore, we suggested that kaempferol might regulate a suitable level of estrogenic activity in the body and is expected to have potential beneficial effects in preventing estrogen imbalance diseases (breast cancer, osteoporosis, cardiovascular disease and etc.).

• The Korea Journal of Herbology
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• v.35 no.3
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• pp.1-8
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• 2020

Objectives : In this study, we examined the estrogenic activities and anti-osteo clastogenesis effects of PCE17, a mixture of PE (an extract of Puerariae Flos), and CE (an extract of Citri Unshius Pericarpium). Methods : The estrogenic effect of PCE17, PE and CE were examined by ER-β/ERE reporter gene assay and proliferation assay in 293 T and MCF-7 cells. The expression of estrogen-responsive gene and protein were checked by Real Time-PCR (RT-PCR) and Western blotting in MCF-7 cells. Inhibitory effect of PCE17, PE and CE on RANKL-induced osteoclast differentiation were evaluated by TRAP staining and RT-PCR in primary osteoclast precursors from rat bone marrow cells. Results : PCE17 and PE bind to ERs (estrogen receptors) and show estrogenic activities in 293T cells. They also stimulated the proliferation of MCF-7 cells and increased the expression of ER response gene, pS2. Tectorigenin, an active ingredient of PE, shows similar estrogenic activities in MCF-7 cells. PCE17 and CE inhibited RANKL-induced osteoclastogenesis in rat primary osteoclast precursor cells and down-regulated the osteoclast-specific genes of Nfatc1, Ctsk, and Acp5. Conclusions : In conclusion, PCE17 may have therapeutic potential in cases of menopause and osteoporosis.

• Journal of Life Science
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• v.9 no.2
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• pp.19-23
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• 1999

Bisphenol-A and related conpounds recently have been reported to be estrogenic since it has been demonstrared in laboratory stuides that they mimic the effects of estrogen. Bisphenol-A refered to as "environmental estrogen" are suspected of causing health effect in living body through disruption of endocdrine system. In this review, the occurrence, environmental fate, and biological effects of bisphenol-A are presented. To provide understanding to the potential for endocrine disruption due to environmental estrogen, the physiology of bisphenol-A mammalian and fish is also reviewed. For empty can, the migrationof bisphenol-A form food conducted epoxy coating was effected by the test conditions and it increased in order to water and 4% acetic acid. Extracts from foods packed in lacquer coated can also showed estrogenic activity. Bisphenol-A was found as a contaminant not only in the liquid food cans, but also in water autoclave in can. The used of coating certain food-packaging material may require closer scrutiny to determine when bisphenol-A contribute to advert exposure of consumers to estrogenic xenobiotics. Human breast cancer MCF cell added bisphenol-A cultivated to study the ability of bisphenol-A to elicit of bisphenol-A estrogenic bioresponse in this system. Bisphenol-A, similar to estradiol, induced PR activation in transiently transfected anterior and posterior pituitary cells.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.185-189
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• 2007

Gene expression levels of choriogenin, vitellogenin and estrogen receptor were determined using Reverse transcription (RT)-PCR technique after exposure to estrogenic chemical bisphenol A in the Korean wild medaka (Oryzias sinensis). These genes have been known to be induced in male test fish when the fish are exposed to estrogenic chemicals. Therefore they can be suggested as a possible biomarker of endocrine disruption in fish, however, relatively little has been known about these genes expression by estrogenic chemicals in Korean wild fish. Mature male Oryzias sinensis were treated with bisphenol A at nominal concentrations of 0.02, 0.2 and 2 mg/L for 6 days and total RNA was extracted from the livers of treated fish for RT-PCR. When the five biomarker genes were amplified by RT-PCR in the same condition, mRNA induction level of each gene was elevated with different sensitivities. Conclusively, the results of this work indicated that measurement of vitellogenin and choriogenin using RT-PCR is effective as a simple tool for the screening of estrogenic chemicals and suggested that O. sinensis would be a suitable model fish for the environmental risk assessment of potential endocrine disruptors.