• Toxicological Research
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• 제17권1호
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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.

• Animal cells and systems
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• 제11권1호
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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.

• Toxicological Research
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• 제22권1호
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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.

• 대한한방소아과학회지
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• 제15권1호
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• pp.105-115
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• 2001

The relation of endocrine in the western medicine and zangfu-organ functions in Korean medicine, related to growth disturbance, was studied and derived the following results. 1. The hormone most related to growth disturbance is, directly secreted from the anterior pituitary or is stimulated and secreted in the target grands, growth hormone, thyroid, adrenocortical hormone, gonadial hormone and is insulin secreted from $\beta$ cell of langerhans' slands of pancreas. 2. the pituitary has the most close relation with the kidney in the five zang-organ. Because the kidney is innate origin(先天之本) and promotes qi and blood(生化氣血), stores the essence of life(藏精), dominates the bones(主骨) and promotes the marrow(生骨髓). Especially it is connected with brain(通於腦). 3. In the children growth, the endocrine action in the pituitary has the most close relation with the kidney, As in the reports of the brain and spinal cord, bone, store essence of life, sexual maturation and decline(kidney-qi, sexual functions of both sexes(天癸)) etc, and cause of cretinism, dwarf in the main subject. 4. Somatomedin is the most important factor of the growth factors, IGF in another word. The unification of IGF and secretion is controlled firstly according to growth hormone, however is very closely related to the nutrition status in the non-hormonic causes. Also, it is affected very much by the insulin. 5. Insulin is one of the important hormone related to the growth and is secreted from the pancreas. Pancreas belongs to the functional system of spleen in oriental medicine, thus the growth disturbance, occurred due to error in insulin secretion and nutrition(in another words, the lack of postnatal essential substance from food-stuff(水穀精氣)), is closely related to the spleen. 6. From the results driven above, the hormone action of endocrine and problem in secretion, related to the growth disturbance, must be focused on the differentiation of symptoms and signs of the kidney and the spleen in oriental medicine.

• 한국환경보건학회:학술대회논문집
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• 한국환경보건학회 2004년도 International Conference Current Challenges and Advances in Environmental Health
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• pp.86-87
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• 2004

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.67-67
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• 2003

Tributyltin chloride (TBTCI) is an organotin compounds that have been widely used as antifouling agents and bioaccumulated in the food chain. TBTCI has been known to induce imposex in female gastropods. There are several reports that TBTCI increased testosterone level and inhibited the conversion of testosterone to estradiol by the aromatase cytochrome P450 enzyme. In this studies, we investigated the effects of TBTCI on steroidogenesis in testes, We dosed to 4-week-old Spragus-Dawleys (SD) male rats with TSTCI (0, 1, 5, 10, and 20mg/kg/day) daily by gavage for 14 days. TBTCI significantly decreased the weights of seminal vesicle, prostate, cowper's gland and LABC at 10 and 20mg/kg/day but significantly Increased the weights of liver at 10 and 20mg/kg/day and adrenals at 20mg/kg/day. mRNA levels of steroidogenic acute regulatory (StAR) and P450 aromatase were decreased and mRNA levels of cytochrome P450 17$\alpha$-hydroxylase/$C_{17-20}$ lyase (P450c17) were increased by TBTCI. TBTCI significantly increased serum testosterone level in dose-dependent manner. From above results, we found that TBTCI altered mRNA levels of enzymes related steroidogenesis, weights of organs and serum testosterone levels. This suggests that change of hormone levels may be due to alteration of mRNA levels of steroidogenic enzyme in testes, but further studies are necessary to investigate hormone levels in testis organ in order to find a relation of enzyme related to steroidogenesis with hormone levels. This work was supported by the Korea FDA Grant KFDA-03131-EDS-010.

• 한국동물학회:학술대회논문집
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• 한국동물학회 2000년도 한국생물과학협회 학술발표대회
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• pp.186.2-186
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• 2000

No Abstract, See Full Text

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 춘계학술대회
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• pp.180-180
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• 2003

Transcript profiling is a particularly valuable tool in the field of steroid receptor biology, as these receptors are ligand-activated transcription factors and therefore exert their initial effects through altering gene expression in responsive cells. Also, an increased awareness of endocrine disrupting chemicals (EBCs) and their potential to affect wildlife and humans has produced a demand for practical screening methods to identify endocrine activity. Here we developed an in-house cDNA microarray, named KISTCHIP-400, with 401 clones, hormone related genes, factors, and ESTs, based on public database and research papers. Theses clones contained estrogen, androgen, thyroid hormone St receptors, sex hormone signal transduction ＆ regulation, c-fos, c-myc, ps2 gene, metabolism related genes etc. And to validate the KISTCHIP-400, we investigated gene expression profiles with reference hormones, 10$\^$-8/ M 17be1a-estradiol, 10$\^$-7/ M testosterone, 10$\^$-7/ M progesterone, and thyroxin in MCF-7 cell line. Although it is in first step of validation, low doses and combinations of EDCs need to be tested. Our preliminary results that indicate the developed microarray may be a useful laboratory tool for screening EDCs and elucidating endocrine disrupting mechanism.

• Clinical and Experimental Pediatrics
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• 제55권7호
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• pp.224-231
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• 2012

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder characterized by hypothalamic-pituitary dysfunction. The main clinical features include neonatal hypotonia, distinctive facial features, overall developmental delay, and poor growth in infancy, followed by overeating with severe obesity, short stature, and hypogonadism later in development. This paper reviews recent updates regarding the genetic aspects of this disorder. Three mechanisms (paternal deletion, maternal disomy, and deficient imprinting) are recognized. Maternal disomy can arise because of 4 possible mechanisms: trisomy rescue (TR), gamete complementation (GC), monosomy rescue (MR), and postfertilization mitotic nondisjunction (Mit). Recently, TR/GC caused by nondisjunction at maternal meiosis 1 has been identified increasingly, as a result of advanced maternal childbearing age in Korea. We verified that the d3 allele increases the responsiveness of the growth hormone (GH) receptor to endogenous GH. This paper also provides an overview of endocrine dysfunctions in children with PWS, including GH deficiency, obesity, sexual development, hypothyroidism, and adrenal insufficiency, as well as the effects of GH treatment. GH treatment coupled with a strictly controlled diet during early childhood may help to reduce obesity, improve neurodevelopment, and increase muscle mass. A more active approach to correct these hormone deficiencies would benefit patients with PWS.

• Molecular & Cellular Toxicology
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• 제1권1호
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• pp.52-61
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• 2005

Transcript profiling is a particularly valuable tool in the field of steroid receptor biology, as these receptors are ligand-activated transcription factors and therefore exert their initial effects through altering gene expression in responsive cells. Also, an awareness of endocrine disrupting chemicals (EDCs) and their potential screening methods to identify endocrine activity have been increased. Here we developed an in-house cDNA microarray, named KISTCHIP-400 ver. 1.0, with 416 clones, based on public database and research papers. These clones contained estrogen, androgen, thyroid hormone & receptors, sex hormone signal transduction & regulation, c-fos, c-myc, ps2 gene, metabolism related genes etc. Also, to validate the KISTCHIP-400 ver. 1.0, we investigated gene expression profiles with reference hormones, $10^{8}\;M\;17{\beta}-estradiol,\;10^{-7}\;M\;testosterone\;and\;10^{-7}\;M$ progesterone in MCF-7 cell line. As the results, gene expression profiles of three reference hormones were distinguished from each other with significant and identified 33 $17{\beta}-estradiol$ responsive genes. This study is in first step of validation for KISTCHIP-400 ver. 1.0, as following step transcriptional profile analysis on not only low concentrations of EDCs but suspected EDCs using KISTCHIP-400 ver. 1.0 is processing. Our results indicate that the developed microarray may be a useful laboratory tool for screening EDCs and elucidating endocrine disrupting mechanism.