• Environmental Mutagens and Carcinogens
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• v.22 no.3
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• pp.175-182
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• 2002

Endocrine disruptors (EDs) are the chemicals that affect endocrine systems through activation or inhibition of steroid hormone response. It is necessary to have a good system to evaluate rapidly and accurately endocrine-disrupting activities of suspected chemicals and their degradation products. The key targets of EDs are nuclear hormone receptors, which bind to steroid hormones and regulate their gene transcription. We constructed a co-expression system of Gal4p DNA binding domain (DBD)- ligand binding domain of human estrogen receptor $\alpha$ or $\beta$, and Gal4p transactivation domain (TAD)-co-activator AIB-1, SRC-1 or TIF-2 in Saccharomyces cerevisiae with a chromosome-integrated lacZ reporter gene under the control of CYC1 promoter and Gal4p binding site (GAL4 upstream activating sequence, GAL4$_{UAS}$). Expression of this reporter gene was dependent on the presence of estrogen or EDs in the culture medium. We found that the two-hybrid system with combination of the hER$\beta$ LBD and co-activator SRC-1 was most effective in the xenoestrogen-dependent induction of reporter activity. The extent of transcriptional activation by those chemicals correlated with their estrogenic activities measured by other assay systems, indicating that this assay system is efficient and reliable for measuring estrogenic activity. The data in this research demonstrated that the yeast detection system using steroid hormone receptor and co-activator is a useful tool for identifying chemicals that interact with steroid receptors.s.

• Molecules and Cells
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• v.45 no.11
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• pp.771-780
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• 2022

The field of extracellular vesicles (EVs) has expanded tremendously over the last decade. The role of cell-to-cell communication in neighboring or distant cells has been increasingly ascribed to EVs generated by various cells. Initially, EVs were thought to a means of cellular debris or disposal system of unwanted cellular materials that provided an alternative to autolysis in lysosomes. Intercellular exchange of information has been considered to be achieved by well-known systems such as hormones, cytokines, and nervous networks. However, most research in this field has searched for and found evidence to support paracrine or endocrine roles of EV, which inevitably leads to a new concept that EVs are synthesized to achieve their paracrine or endocrine purposes. Here, we attempted to verify the endocrine role of EV production and their contents, such as RNAs and bioactive proteins, from the regulation of biogenesis, secretion, and action mechanisms while discussing the current technical limitations. It will also be important to discuss how blood EV concentrations are regulated as if EVs are humoral endocrine machinery.

• Animal cells and systems
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• v.11 no.1
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• pp.1-8
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• 2007

Recently, we have shown that some endocrine disruptors, heavy metals, organotins and azoles suppressed steroidogenic enzymes such as P450 side-chain cleavage enzyme (P450scc) and aromatase in bullfrog ovarian follicles. In the present study, by using an amphibian ovarian follicle culture system, we examined the effects of these endocrine disruptors on maturation and ovulation of oocytes from Rana dybowskii in vitro. Ovarian fragments or isolated follicles were cultured for 24 h in a medium containing frog pituitary homogenate (FPH) or progesterone ($P_{4}$) with or without endocrine disruptors, and oocyte maturation (germinal vesicle breakdown, GVBD) and ovulation were examined. Among the organotins, tributyltin (TBT) strongly inhibited both FPH-and $P_{4}-induced$ oocyte maturation ($ED_{50}$:0.6 and 0.7 ${\mu}M$, respectively); however, tetrabutyltin (TTBT) and dibutyltin (DBT) showed only partial suppression, while monobutyltin (MBT) showed no inhibitory effect. All of the organotins suppressed $P_{4}-induced$ oocyte ovulation very effectively at a low concentration, and TBT and DBT exerted an inhibitory effect on FPH-induced ovulation. Among the heavy metals, mercury (Hg), cadmium (Cd) and cobalt (Co) were very effective in inhibiting FPH-induced oocyte maturation and ovulation, while lead (Pb), arsenite (As) and zinc (Zn) were less effective. However, all of the heavy metals suppressed FPH-induced oocyte ovulation at a high dose ($100{\mu}M$). Among the azoles, itraconazole (ICZ), ketoconazole (KCZ) and clotrimazole (CTZ) effectively inhibited FPH-induced oocyte maturation and ovulation, while econazole (ECZ), miconazole (MCZ) and fluconazole (FCZ) were considerably less effective. These results demonstrated that the abovementioned endocrine disruptors exhibited differential effects on oocyte maturation and ovulation in amphibian follicles and that the frog ovarian culture system could be used as an effective experimental tool to screen and evaluate the toxicity of various endocrine disruptors in vitro.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.5937-5946
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• 2012

The term endocrine disruptors is used to describe a variety of natural and manmade substances that have the capacity to potentially interfere with and modify the normal physiology of endocrine system either by mimicking, blocking or modulating the actions of natural endogenous hormones. The rising incidence of breast cancer over the last 50 years and the documented higher incidence in urban as compared to rural areas suggest a relationship to the introduction and increased use of xenoestrogens in our environment. The literature has developed over the last decades where initial experiments on endocrine disruptors did not support an involvement in breast cancer, and then evidence mounted implicating various environmental factors including hormones, endocrine disrupting chemicals and non-endocrine disrupting environmental carcinogens in the pathogenesis of breast cancer. Available data support the hypothesis that exposure to endocrine disruptors in utero leaves a signature on mammary gland morphogenesis so that the resulting dysgenic gland becomes more predisposed to develop tumors upon exposures to additional insults later on during life. Exceptionally, exposure to phytoestrogens could be beneficial to human health. Most of the available data are from well developed countries while the developing countries are still understudied regarding these issues. Here, we raise a note of caution about potential role of environmental toxins including endocrine disruptors in breast cancer development and call for serious measures to be taken by all involved parties in the developing world.

• Toxicological Research
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• v.17 no.1
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• pp.65-71
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• 2001

The key targets of endocrine disruptors are nuclear hormone receptors, which bind to steroid hormones and regulate their gene transcription. A yeast-based steroid hormone receptor gene trascription assay was previously developed for the evaluation of chemicals with endocrine modulating activity. The yeast transformants used in this assay contain the human estrogen receptor along with the appropriate steroid response elements upstream of the $\beta$-galactosidase reporter gene. We tried to evaluate several natural and synthetic steroids of their potential to interact directly with the steroid receptor. Some putative endocrine disruptors, including nonylphenol, are weakly estrogenic. But the combined treatment oj these chemicals with di-(2-ethylhexyl)phthalate (DEHP) significantly increased the $\beta$-galactosidase activity in the yeast transformant. These results suggest that we also have to consider the synergistic effects of endocrine disruptors. In this study, we showed that yeast-based bioassay is a valuable tool for screening potential endocrine disruptors and quantitative determination of estrogenicity. And the possibility that the estrogen receptor binds multiple environmental chemicals adds another level of complexity to the interaction between the endocrine disruptors and the human hormone system.

• Proceedings of the KOSOMBE Conference
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• v.1991 no.11
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• pp.113-118
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• 1991

Hypertension is a medical problem with no permanent cure. Extended hypertension can cause various cardio vascular diseases, cerebral vascular diseases, and circulatory system trouble. Medical treatment at present does not consider circadian variation of blood pressure in patients ; therefore, the problem of over-reduction of blood pressure through drugs sometimes occurs. This paper presents a prediction model of circadian variation or moon blood pressure employing the endocrine grand and the autonomic nervous system.

• Clinical and Experimental Reproductive Medicine
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• v.46 no.3
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• pp.99-106
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• 2019

Bisphenol A (BPA) is an endocrine-disrupting chemical that is capable of interfering with the normal function of the endocrine system in the body. Exposure to this chemical from BPA-containing materials and the environment is associated with deleterious health effects, including male reproductive abnormalities. A search of the literature demonstrated that BPA, as a toxicant, directly affects the cellular oxidative stress response machinery. Because of its hormone-like properties, it can also bind with specific receptors in target cells. Therefore, the tissue-specific effects of BPA mostly depend on its endocrine-disrupting capabilities and the expression of those particular receptors in target cells. Although studies have shown the possible mechanisms of BPA action in various cell types, a clear consensus has yet to be established. In this review, we summarize the mechanisms of BPA action in spermatozoa by compiling existing information in the literature.

• Journal of Embryo Transfer
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• v.28 no.2
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• pp.95-111
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• 2013

Worldwide there is concern about the continuing release of a broad range of environmental endocrine disrupting chemicals, including polychlorinated biphenyls, dioxins, phthalates, polybrominated diphenyl ethers (PBDEs), and other halogenated organochlorines persistent organic pollutants (POPs) into the environment. They are condemned for health adverse effects such as cancer, reproductive defects, neurobehavioral abnormalities, endocrine and immunological toxicity. These effects can be elicited via a number of mechanisms among others include disruption of endocrine system, oxidation stress and epigenetic. However, most of the mechanisms are not clear, thus several number of studies are ongoing trying to elucidate them in order to protect the public by reducing these adverse effects. In this review, we briefly limited review the process, the impacts, and the potential mechanisms of dioxin/dioxin like compound, particularly, their possible roles in adverse developmental and reproductive processes, diseases, and gene expression and associated molecular pathways in cells.

• Toxicological Research
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• v.22 no.1
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• pp.15-22
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• 2006

Many of endocrine disrupting chemicals induce effects via interaction with hormone receptors and responsive elements in target cells. We investigated endocrine disrupting effects of some food additives and contaminants including BHA, BHT, ethoxyquin, propionic acid, sorbic acid, benzoic acid, CPM, aflatoxin B1, cadmium chloride, genistein, TCDD and PCBs in yeast transformants expressing human steroid hormone receptors along with steroid responsive elements. The response limit of genetically recombinant yeast to $17{\beta}$-estradiol, testosterone and progesterone was $1{\times}10^{-16},\;1{\times}10^{-12}\;and\;1{\times}10^{-13}M$, respectively. BHT induced weak transcriptional activity in estrogen sensitive yeast, while BHA and sorbic acid interacted weakly with androgen receptor/responsive element. CPM induced transcriptional activities in all types of yeasts sensitive to steroid hormones. Zearalenone and genistein induced high transcriptional activation in estrogen sensitive yeast with relative potencies almost $10^8$ folds lower than $17{\beta}$-estradiol. TCDD induced transcriptional activation weakly in estrogen- and progesterone- sensitive yeasts. This study elucidated that recombinant yeast is a sensitive and high-throughput system and can be used for the direct assessment on chemical interactions with steroid receptors and responsive elements. Also, the present study raises the requirement of evaluation on the endocrine disrupting effects of BHT, BHA, sorbic acid, CPM and TCDD for their transcription activity in yeast screening system though weak in intensity.

• Journal of Life Science
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• v.32 no.1
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• pp.70-77
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• 2022

Endocrine disrupting chemicals (EDCs) have been attracting significant attention in modern society, owing to the increased incidence rate of various diseases along with population growth. EDCs are found in many commercial products, including some plastic bottles and containers, detergents, liners of metal food cans, flame retardants, food, toys, cosmetics, and pesticides. EDCs have a hormonal effect on the human body, which disrupts the endocrine system, notably affecting sexual differentiation and normal reproduction, and can trigger cancer as well. Recently, the association between neurological diseases and EDCs has become a hot topic of research in the field of neuroscience. Considering that EDCs negatively affect not only neuronal proliferation and neurotransmission but also the formation of the neuronal networks, EDCs may induce neurodevelopmental disorders, such as autism spectrum disorders and attention-deficit/hyperactivity disorder as well as neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. In light of these potentially deleterious outcomes, important efforts have been underway to minimize the exposure to EDCs through appropriate regulations and policies around the world, but chemicals that have not yet been associated with endocrine disrupting properties are still in wide use. Therefore, more epidemiological investigations and research are needed to fully understand the effects of EDCs on the nervous system.