• Toxicological Research
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• v.17 no.3
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• pp.203-213
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• 2001

We investigated the toxic effects of propylthiouracil (PTU) In Sprague-Dawley (SD) rats to develop and validate an enhanced Protocol for Test Guideline 407 as OECD Project. Twenty male and female SD rats,7 weeks old, were treated with PTU in corn oil at levels of 0, 0.1, 1 and 10 mg/kg/day for 4 weeks orally. Clinical observation, body weight changes, food uptake, water consumption, urinalysis, estrus cycle and sperm analysis, serum chemist교, autopsy findings and histopathological findings were evaluated in this study. No clinical signs and mortality were observed in the study. The body weights and food uptakes in the group treated with 10 mg/kg/day were reduced from 3 weeks after the initiation of the treatment. The levels of 3,5,3'-triiodothyronine (T3) and thyroxine (T4, 3,5,3',5'-tetraiodothyrosine) were also significantly decreased in the group treated with 10 mg/kg/day. Also, the relative and absolute organ weights of thymuses were decreased. Thyroid glands of rats in the group treated with PTU 10 mg/kg/day were bigger than those of rats in the control group. In the histopathological examination, diffuse hyperplasia and hypertrophy of thyroid follicular cells were observed in all treatment groups, leading to the reduction of lumen size and papillary enfolding of lining epithelium. The degree of lesion was increased in a dose-dependent manner. The results suggested that PTU would cause toxicity in thyroid gland and decrease the levels of T3 and T4 in SD rats. However there were no effects on the other organ including testis and uterus especially in spermatogenesis and estrus cycle. On the basis of the results, enhanced protocol for Test Guideline (TG) 407 may be sensitive and reliable to detect endocrine-active substances like PTU.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.503-511
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• 2018

Triclosan (TCS) and bisphenol A (BPA) are endocrine-disrupting chemicals that interfere with the hormone or endocrine system and may cause cancer. Kaempferol (Kaem) and 3,3'-diindolylmethane (DIM) are phytoestrogens that play chemopreventive roles in the inhibition of carcinogenesis and cancer progression. In this study, the influence of TCS, BPA, Kaem, and DIM on proliferation and apoptotic abilities of VM7Luc4E2 breast cancer cells were examined. MTT assay revealed that TCS ($0.1-10{\mu}M$), BPA ($0.1-10{\mu}M$) and E2 ($0.01-0.0001{\mu}M$) induced significant cell proliferation of VM7Luc4E2 cells, which was restored to the control (0.1% DMSO) by co-treatment with Kaem ($30{\mu}M$) or DIM ($15{\mu}M$). Reactive oxygen species (ROS) production assays showed that TCS and BPA inhibited ROS production of VM7Luc4E2 cells similar to E2, but that co-treatment with Kaem or DIM on VM7Luc4E2 cells induced increased ROS production. Based on these results, the effects of TCS, BPA, Kaem, and DIM on protein expression of apoptosis and ROS production-related markers such as Bax and Bcl-xl, as well as endoplasmic reticulum (ER) stress-related markers such as $eIF2{\alpha}$ and CHOP were investigated by Western blot assay. The results revealed that TCS, and BPA induced anti-apoptosis by reducing ROS production and ER stress. However, Kaem and DIM effectively inhibited TCS and BPA-induced anti-apoptotic processes in VM7Luc4E2 cells. Overall, TCS and BPA were revealed to be distinct xenoestrogens that enhanced proliferation and anti-apoptosis, while Kaem and DIM were identified as natural chemopreventive compounds that effectively inhibited breast cancer cell proliferation and increased anti-apoptosis induced by TCS and BPA.

• Clinical and Experimental Reproductive Medicine
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• v.21 no.3
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• pp.253-259
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• 1994

A clinical investigation was undertaken on primary male infertility patients of recent 5 years. The results obtained were as follow: 1. Suspective etiologic factors were: 1) testicular failure, 36.1 %; 2) varicocele, 18.7%; 3) endocrine abnormality, 13.5%; 4) obstruction, 13.5%; 5) idiopathic, 10.9%; 6) cryptorchidism, 2.6%; 7) necrospermia, 0.9%. 2. On semen analyses, azoospermia was found in 55.8%, single abnormal parameter in 21.5 %, and multiple/all abnormal parameter in 22.7% of the 163 cases. 3. For the evaluation of the sensitivity and specificity of noninvasive variables in predict in obstruction as the cause of azoospermia in patient who had undergone testicular biopsy, the testicular size and serum follicle-stimulating hormone(FSH) level revealed 100% of sensitivity. 4. Among the 43 patients with a testicular biopsy confirmed diagnosis there was a significant difference in testicular size, ejaculate volume(p<0.0001) and serum FSH(p<0.0001) between patients with testicular failure and those with ductal obstruction. 5. Of 93 treated patients with primary male infertility, 42 were managed by medical treatment including endocrine treament, retrograde ejaculation treatment, infection treatment and observation; 29 were managed by surgical treatment including varicocelectomy, vasovasostomy, vasoepididymostomy and TUR of ejaculatory duct; 20 were managed by sperm preparation treatment including artificial insemination(AI), electroejaculation plus AI and vibration ejaculation plus AI ; 2 were managed by microscopic epididymal sperm aspiration plus IVF, repectively. 6. 42 patients who could be followed-up, 21 patients(50%) impregnated their wives.

• Applied Biological Chemistry
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• v.49 no.3
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• pp.196-201
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• 2006

Vitellogenin, which is found in the serum of female and male fishes exposed to environmental endocrine disrupter or estrogen hormone, is used as a biomarker for environmental contamination with an endocrine disrupter. In order to produce antibody against vitellogenin, a synthetic peptide for partial vitellogenin was injected into rabbits. In addition, by using ion exchange chromatography on DE-52, vitellogenin was purified from the serum of carp induced with $17{\beta}$-estradiol. Polyclonal antibody against purified vitellogenin reacted well with vitellogenin in the serum of carp induced with $17{\beta}$-estradiol and the serum of female carp, whereas polyclonal antibody against the vitellogenin peptide did not react with proteins in those samples. This may indicate that vitellogenin proteins, covalently modified largely, could not be detected by Western blotting with the polyclonal antibody against the synthetic vitellogenin peptide.

• Journal of East-West Nursing Research
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• v.28 no.2
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• pp.100-108
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• 2022

Korean medicine has traditionally provided a lot of medical care for the treatment of infertility. The combination treatment of Korean medicine and Western medicine can be effective for infertility to improve the problems caused by the extremely low fertility rate and the aging of pregnant women. In relation to female infertility, we reviewed the evidence for Korean medicine treatment for polycystic ovary syndrome, which has recently been increasing interest in female infertility, and the evidence for the collaboration between Korean and Western medicine in the treatment of polycystic ovary syndrome and infertility. Because polycystic ovary syndrome is closely related to metabolic diseases related to endocrine abnormalities, hormone treatment alone has limited therapeutic effects and has side effects. In domestic and international research, herbal medicine and acupuncture in the treatment of infertility have shown good clinical effects based on the hypothesis of various mechanisms of effect, and many cases of successful pregnancy have been reported. Although continuous research through large-scale randomized clinical studies is needed to prove efficacy, the importance of combined treatment of Korean medicine and Western medicine in infertility treatment is increasing in order to solve the extremely low fertility rate. Combining artificial insemination or in vitro fertilization with Korean medicine treatment is highly likely to be effective in increasing pregnancy success and fertility rates. In women with polycystic ovary syndrome, which is recognized as a metabolic disease due to endocrine abnormalities among the causes of female infertility, Korean medicine treatment can increase the pregnancy rate with herbal medicines and acupuncture, etc. Although well-designed large-scale clinical studies are currently lacking and meta-analysis has not provided sufficient evidence, the combination treatment of Korean medicine and Western medicine is more active to increase the pregnancy rate for solving the problem of low fertility.

• Development and Reproduction
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• v.27 no.4
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• pp.185-193
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• 2023

Although increasing evidence of cause-and-effect relationship between BPA exposure and female reproductive disorders have been suggested through many studies, the precise biochemical and molecular mechanism(s) by which BPA interferes with steroidogenesis in the ovarian cells still remain unclear. Therefore, the purpose of this study was to discover the steroidogenic biomarker(s) associated with BPA treatment in human granulosa cell line, KGN. In this study, our results obtained via the analysis of steroidogenesis-related protein expression in KGN cells using quantitative polymerase chain reaction (qPCR) and western blot analyses revealed that the expression levels of steroidogenic acute regulatory (StAR) and aromatase decreased considerably and gradually after BPA treatment in a dose-dependent manner under BPA treatment. Further, remarkable decreases in their expression levels at the cellular levels were also confirmed via immunocytochemistry, and subsequent StAR and aromatase mRNA expression levels showed profiles similar to those observed for their proteins, i.e., both StAR and aromatase mRNA expression levels were significantly decreased under BPA treatment at concentrations ≥0.1 μM. We observed that follicle stimulating hormone upregulated StAR and aromatase protein expression levels; however, this effect was suppressed in the presence of BPA. Regarding the steroidogenic effects of BPA on KGN cells, controversies remain regarding the ultimate outcomes. Nevertheless, we believe that the results here presented imply that KGN cells have a good cellular and steroidogenic machinery for evaluating endocrine disruption. Therefore, StAR and aromatase could be stable and sensitive biomarkers in KGN cells for the cellular screening of the potential risk posed by exogenous and environmental chemicals to female reproductive (endocrine) function.

• The Korean Journal of Physiology and Pharmacology
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• v.70 no.3
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• pp.435-442
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• 2019

Endocrine-disrupting chemicals (EDCs) have structures similar to steroid hormones and can interfere with hormone synthesis and normal physiological functions of reproductive organs. For example, sex steroid hormones influence calcium signaling of the cardiac muscle in early embryo development. To confirm the effect of progesterone (P4), octyl-phenol (OP), and bisphenolA(BPA) on early differentiation of mouse embryonic stem cells(mESCs) into cardiomyocytes, mESCs were treated with P4, OP, and BPA two days after attachment and media were replaced every two days. In addition, cells were treated with mifepristone (RU486), a synthetic steroid that has an affinity for progesterone receptor (Pgr), for one day starting on day 11. Beating ratio was decreased with P4, OP, and BPA treatment. The Pgr mRNA level was significantly increased in the P4-, OP- and BPA-treated groups. However, the mRNA level of the calcium channel gene (Trpv2), contraction-related genes (Ryr2, Cam2, and Mylk3) and cardiac development and morphogenesis genes (Rbp4, Ly6e, and Gata4) were significantly decreased in the P4-, OP-, and BPA-treated groups. Interestingly, treatment with RU486 rescued the altered calcium channel gene, contraction-related genes, and cardiac development and morphogenesis genes. P4, OP, and BPA treatments reduced the intracellular calcium level. Taken together, these results indicate that EDCs (OP and BPA) has a structure similar to that of endogenous steroid hormones such as progesterone and estrogen, and OP and BPA act like progesterone to inhibit and disrupt cardiomyocyte differentiation of mESCs.

• The Journal of Internal Korean Medicine
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• v.26 no.1
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• pp.213-220
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• 2005

Objective : Thyroid diseases are one of the most common endocrine disorders. However, the first chosen-treatments including anti-thyroidal and hormone-supplement therapy in western medicines, sometimes have failed to improve abnormal thyroid hormone secretions and clinical symptoms. Therefore, there has been a growing expectation for Oriental Medicine to take the role of alternative therapy. However, there has been little analysis of clinical characteristics. In this study, clinical characteristics of thyroidal disease patients who visited Kyung-Hee oriental hospital from January to July 2004 were analyzed. Methods : A total 86 patients diagnosed as hyperthyroidism, hypothyroidism or thyroid nodule were selected. Clinical history, including sex, age, symptoms, disease duration and methods of previous therapy and thyroidal test, such as thyroid function test (TFT), thyroid scan and other thyroid examinations. Results : In distribution of onset age and sex, the patients who have visited oriental hospital with thyroidal diseases showed similar characteristics with typical patients. In clinical symptom, the most frequent clinical sign was fatigue in both hyperthyroidism and hypothyroidism, which differs from the classical characteristics of those diseases. Most patients complained the unresolved symptoms, some of which are attributable to abnormal thyroid hormone secretions, in spite of western therapy with anti-thyroidal and hormone supplement agents. Conclusions : In oriental therapy, it will be necessary to consider the unique clinical features of thyroidal diseases different from classical patterns, and this study suggests that oriental therapy is a good alternative method for patients whose first treatment with western agents failed. Furthermore, more public information to these patients about oriental medicine would be helpful to increase cure rates, and give various choices to patients with thyroid diseases.

• Korean journal of applied entomology
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• v.61 no.1
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• pp.109-115
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• 2022

Vitellogenesis is the process by which yolk accumulates in developing oocytes. The initiation of vitellogenesis represents an important control point in oogenesis. When females of the model insect Drosophila melanogaster molt to become adults, their ovaries lack mature vitellogenic oocytes, only producing them after reproductive maturation. After maturation, vitellogenesis stops until a mating signal re-activates it. Juvenile hormone (JH) from the endocrine organ known as the corpora allata (CA) is the major insect gonadotropin that stimulates vitellogenesis, and the seminal protein sex peptide (SP) has long been implicated as a mating signal that stimulates JH biosynthesis. In this review, we discuss our new findings that explain how the nervous system gates JH biosynthesis and vitellogenesis associated with reproductive maturation and the SP-induced post-mating response. Mated females exhibit diurnal rhythmicity in oogenesis. A subset of brain circadian pacemaker neurons produce Allatostatin C (AstC) to generate a circadian oogenesis rhythm by indirectly regulating JH and vitellogenesis through the brain insulin-producing cells. We also discuss genetic evidence that supports this model and future research directions.

• Journal of Environmental Health Sciences
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• v.46 no.4
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• pp.368-375
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• 2020

Objectives: Some animal studies have reported that methyl mercury causes developmental toxicities such as placental and fetal weight loss, but the mechanism is still unclear. This study aimed to investigate the developmental toxicities of methyl mercury, focusing on placental endocrine function and fetal growth retardation in rats. Methods: Positively same-time-mated female Sprague-Dawley rats were purchased on gestational day (GD) eight and treated with 0, 5, 10 and 20 ppm of methyl mercury (n=5) dissolved in tap water from GD eight through 19. During treatment, the drinking water (methyl mercury) intake and body weight of each pregnant rat was measured daily. On day 19, caesarean sections were performed and blood samples were collected. Developmental data such as placental and fetal weights, fetus numbers, and placental efficiency (fetal weight/placental weight) were also collected. Placental prolactin-growth hormone (PRL-GH) family, such as placental lactogen (PL) -Iv, II, and prolactin-like protein (PLP) -B, levels in serum were analyzed by ELISA. Also, placental tissues were assigned to histochemistry. Results: The mean cumulative methyl mercury exposure for the 5, 10, and 20 ppm groups were 2.37, 4.63, and 9.66 mg, respectively. The mean daily exposure of the 5, 10, and 20 ppm groups were 0.24, 0.47, and 0.97 mg, respectively. Maternal body weight increased in accordance with GD. There was no significant difference in weight gain among the experimental groups. Histopathologic changes were not observed in placental tissues among the experimental groups. However, mean placental and fetal weights were lower in the 10 and 20 ppm exposed groups compared to the control. Placental efficiency was also lower in the 10 and 20 ppm exposed groups compared to the control. Serum PL-Iv and II levels were lower in the 10 and 20 ppm exposed groups than the control, in accordance with the changing pattern of placental and fetal weights and placental efficiency. Conclusion: The inhibitory effects of methyl mercury on the serum levels of placental PRL-GH family such as PL-Iv and II may be secondary leads to the reduction of placental efficiency and fetal growth retardation in rats.