• Clinical and Experimental Reproductive Medicine
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• 제45권4호
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• pp.154-162
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• 2018

Objective: The fallopian tubes play a critical role in the early events of fertilization. The rapid innate immune defense is an important part of the fallopian tubes. Toll-like receptor 3 (TLR3), as a part of the innate immune system, plays an important role in detecting viral infections. In this basic and experimental study, the effect of sex hormones on the function of TLR3 in the OE-E6/E7 cell line was investigated. Methods: The functionality of TLR3 in this cell line was evaluated by cytokine measurements (interleukin [IL]-6 and IL-1b) and the effects of sex hormones on TLR3 were tested by an enzyme-linked immunosorbent assay kit. Additionally, TLR3 small interfering RNA (siRNA) and a TLR3 function-blocking antibody were used to confirm our findings. Results: The production of IL-6 significantly increased in the presence of polyinosinic-polycytidylic acid (poly(I:C)) as the TLR3 ligand. Using a TLR3-siRNA-ransfected OE-E6/E7 cell line and function-blocking antibody confirmed that cytokine production was due to TLR3. In addition, 17-${\beta}$ estradiol and progesterone suppressed the production of IL-6 in the presence and absence of poly(I:C). Conclusion: These results imply that sex hormones exerted a suppressive effect on the function of TLR3 in the fallopian tube cell line when different concentrations of sex hormones were present. The current results also suggest that estrogen receptor beta and nuclear progesterone receptor B are likely to mediate the hormonal regulation of TLR3, as these two receptors are the main estrogen and progesterone receptors in OEE6/E7 cell line.

• Toxicological Research
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• 제20권3호
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• pp.205-211
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• 2004

Concern that some chemicals in our environment may affect human health by disrupt-ing normal endocrine function has prompted a research on interactions of environmental contaminants with steroid hormone receptor. Toxaphene and chlordane are among the 12 persistent organic pollutants identified by the United Nations Environment Programme as requiring urgent attention. We compared the estrogenic activity of two organochlorine pesticides, toxaphene and chlordane, at estrogen receptor a (ER$\alpha$) and estrogen receptor $\beta$ (ER$\beta$). Human hepatoma cells (HepG2) were transiently transfected with rat ER$\alpha$ or ER$\beta$ plus an estrogen-responsive complement C3-luciferase (C3-Luc) reporter gene. After transfection, cells were treated with various concentrations of toxaphene and chlordane to investigate agonism or antagonism of these chemicals. Both toxaphene and chlordane were potent agonists in HepG2 cells for ER$\alpha$. In contrast, these chemicals had a minimal agonist activity with ER$\beta$ and almost abolished 17$\beta$-estradiol-induced ER$\beta$-mediated activity. Therefore, toxaphene and chlordane behaved as an ER$\alpha$ agonist and an ER$\beta$ antagonist with estrogen-responsive reporter plasmid C3-Luc, and exposure to these organochlorine pesticides could have a crictical effect on normal endocrine function.

• Asian Pacific Journal of Cancer Prevention
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• 제17권12호
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• pp.5247-5250
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• 2016

Objective: Endometriosis, one of the most common estrogen dependent gynecological disorders, can present as both benign and malignant disease. The prevalence of tumoral transformation is 0.7-1.6% and the most common tumors are clear cell and endometrioid carcinomas. Unfortunately, the pathogenesis of transformation is unknown. For this purpose, we examined molecular alterations in ovarian endometriosis and endometriosis-associated tumors. Methods: Using the data bank of Alzahra hospital pathology department and paraffin blocks from appropriate cases were identified. Sections were cut and stained for 3 markers: estrogen receptor, P53 and bcl2. Correlations between findings were investigated. Results: Nineteen cases of endometriosis-associated tumor and 19 cases of endometriosis were identified. Staining for bcl2 was documented in 14 of 19 (73.7%) of endometriosis-associated tumor cases and also 7 of 19 (36.8%) endometriosis cases (P=0.02). Only 3 of the 19 (15.8%) endometriosis-associated tumors exhibited positive staining for estrogen receptors, compared with 14 of 19 (73.7%) endometriosis cases (P<0.001). Positive staining for P53 was noted in 5 of 19 (31.6%) endometriosis-associated ovarian tumor samples but was absent in endometriosis samples (0%), (P =0.008). Conclusions: Endometriosis-associated tumors appear to be associated with overexpression of bcl2 and P53 and reduced expression of Estrogen receptor. These finding may help to diagnose tumoral transformation with a background of endometriosis.

• BMB Reports
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• 제31권5호
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• pp.419-426
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• 1998

The nuclear hormone receptor superfamily currently includes approximately equal numbers of conventional receptors and orphan receptors, which do not have known ligands. Here, we review recent progress from this laboratory on three orphans, two of which are moving from orphan to conventional receptor status. Perhaps the most unusual is CAR, which is a constitutive transactivator in the absence of ligands but becomes transcriptionally inactive in the presence of its ligands, which are androgen metabolites. The response of CAR to its ligands is thus opposite to that of the conventional receptor paradigm. RIP14 (also known as FXR) is activated by both all-trans retinoic acid and a synthetic retinoid previously thought to specifically target the retinoic acid receptors (RARs), and thus appears to be a novel retinoid receptor. Finally, SHP is a novel orphan that lacks a DNA binding domain and interacts with a number of other receptor superfamily members. While it generally inhibits its targets, including CAR, the retinoid X receptor (RXR), and the estrogen receptor (ER), it stimulates transactivation by the orphan SF-1.

• 미생물학회지
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• 제43권1호
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• pp.54-58
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• 2007

청국장은 미생물, 효소, 다양한 생리활성물질을 포함하는 대두발효식품으로 정장, 핼액순환개선 효과 등이 알려져 있다. 청국장에 존재하는 isoflavone이 유방암, 전립선암의 억제와 관련이 있을 수 있다. 본 연구에서는 HPLC와 Mass 분석을 통해 분말청국장 100% ethanol추출물에 aglycone 형태의genistein, daidzein, glyciten이 존재함을 확인했다. 당이 붙어 있는 genistin, daidzin, OH기가 추가적으로 붙어 있는 8-OH-genistein, 8-OH-daidzein은 존재하지 않았다. Estrogen 수용체에는 $ER{\alpha},ER{\beta}$가 있다. $ER{\alpha}$는 유방암, 전립선암의 촉진에, $ER{\beta}$는 이들 암의 억제와 관련이 있을 것으로 추정한다. 인간의 estrogen 수용체가 cloning되어 있는 효모의 전사촉진 assay를 이용하여, 청국장에 있는 isoflavone이 $ER{\beta}_{1}$를 선택적으로 자극할 수 있음을 확인했다.

• 대한두개안면성형외과학회지
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• 제21권3호
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• pp.176-179
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• 2020

Pilomatricoma is a benign tumor arising from the primitive basal cells of the epidermis that differentiate into hair matrix cells. Mutations in the CTNNB1 gene, which encodes β-catenin (a protein involved in hair growth), play an etiological role in the development of pilomatricoma. A 34-year-old woman presenting with a mass in the right parotid region underwent an excisional biopsy. The mass was conclusively diagnosed as pilomatricoma. During pregnancy, the mass grew from 1 cm to 5 cm in diameter and was accompanied by pain and tenderness. The growth may have been facilitated by the increased production of estrogen and progesterone, which bind to receptors located in the outer root sheath cells of the hair follicles. No recurrence was observed during 6 months of follow-up.

• Journal of Periodontal and Implant Science
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• 제29권1호
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• pp.31-40
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• 1999

Many factors may affect periodontal changes during the physiologic conditions of woman(e.g. puberty, menstrual cycle, pregnancy, menopause). Recently many research has focused on the immunological changes of host, but the exact mechanism is not clear. Collagen is a major constituent of periodontium, and collagenase specifically digests the collagen and plays a role in destruction of periodontal tissue. So, I suppose that it participates with the cytokines in the inflammation of gingiva and vascular response during the changes of female sex hormones. Because there are some evidences of the existence of the receptors of estrogen and progesterone in the gingiva, it may be a target tissue of female sex hormones. In this experiment, gingival fibroblast and periodontal ligament cell were cultured in the presence of various concentrations of estrogen or progesterone corresponding to the menstrual cycle and pregnancy. Collagenase activity of the supernatant of culture media was determined by Spectrophotometric collagenase assay. The enzyme activity was calculated by the % decrease of the coated collagen. 1. The estrogen at both concentrations had no effect on the activity of collagenase of the gingival fibroblast. 2. The progesterone had some effect on the collagenase activity of the gingival fibroblast at low and high concentration of menstrual cycle, and elevated the enzyme activity at all range of pregnancy concentrations. 3. In periodontal ligament cells, estrogen elevated the enzyme activity at the early pregnancy concentration and progesterone elevated at the concentration just before menstruation. In this experiment, pregesterone elevated the collagenase activity of gingival fibroblast and periodontal ligament cells. But the mechanism of the up-regulation of the enzyme activity was not confirmed. The more experiments of direct effect of progesterone on gingival at the molecular level(e.g. northern blot analysis) can reveal the exact mechanism.

• Journal of Ginseng Research
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• 제36권2호
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• pp.169-175
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• 2012

Ginseng has been used as a traditional medicine for treatment of many diseases and for general health maintenance in people of all ages. Ginseng is also used to ameliorate menopausal systems. We investigated the estrogenic activity of Korean red ginseng (KRG) in a transient transfection system, using estrogen receptor (ER) and estrogen-responsive luciferase plasmids in MCF-7 cells. The extract activated both ER${\alpha}$ and ER${\beta}$. KRG modulated the mRNA levels of estrogen-responsive genes such as pS2 and ESR1 and decreased the protein level of ER${\alpha}$. In order to examine in vivo estrogenic activity of KRG, sixteen female Sprague-Dawley rats separated into four groups were studied for nine weeks: non-ovariectomized (OVX) rats treated with olive oil, OVX rats treated with olive oil, OVX rats treated with 17-${\beta}$-estradiol (E2) in olive oil, and OVX rats treated with KRG extract in olive oil. The experiments were repeated for three times and the data of twelve rats were combined. Body weight of OVX rats was greater than that of sham-operated control rats and was decreased by E2 treatment. Uterine weight increased after E2 treatment compared to OVX rats. However, no difference in body or uterine weight was observed with KRG intake. KRG induced reductions in total cholesterol, low density lipoprotein cholesterol/total cholesterol, high density lipoprotein cholesterol/total cholesterol, and low density lipoprotein cholesterol/high density lipoprotein cholesterol, but not to the same degree as did E2 intake. These results show that KRG does contain estrogenic activity as manifested by in vitro study but the activity is not strong enough to elicit physiological responses.

• Archives of Pharmacal Research
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• 제27권1호
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• pp.99-105
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• 2004

Isoflavones have been a central subject in research on the natural phytoestrogens found in Leguminosae. Their effects on bone formation and remodeling are important in that they can act like estrogen by binding on estrogen receptors on the target cell surface. We, therefore, believed that isoflavones may help in the treatment of patients with estrogen deficiency disease such as estrogen replacement therapy (ERT) for osteoporosis. As commonly known, osteoporosis is one of the hormonal deficiency diseases, especially in menopausal women. When estrogen is no longer produced in the body a remarkable bone remodeling process occurs, and the associated events are regulated by growth factors in the osteoblast lineage. In the present study, we investigated whether isoflavones (Isocal) extracted from Sophorae fructus affect the growth factors IGF-I and TGF-$\beta$ that have been known to be related with bone formation. In the study, we found that the active control (PIII) effectively enhanced the level of nitric oxide (NO) and growth factors, and thereby inhibited osteoclastogenesis. The most efficient concentration was $10^{-8}$% within five days, whereas the comparative control (soybean isoflavone) was not as effective even at a lower concentration. In conclusion, the products which contain enriched glucosidic isoflavone and nutrient supplements such as shark cartilage and calcium can be used for osteoporosis therapy by enhancing the production of IGF-I and TGF-$\beta$. Furthermore, the NO produced through endothelial constitutive NO synthase (ecNOS) may playa role in inhibiting bone reabsorption.

• 한국발생생물학회지:발생과생식
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• 제11권3호
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• pp.187-193
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• 2007

Ethane 1,2-dimethane sulfonate(EDS)는 Leydig 세포의 선별적 사멸을 유도하는 약물로서 가역적인 테스토스테론 결핍 흰쥐를 만드는데 널리 사용된다. 부정소의 구조와 기능 유지는 크게 보아 정소에서 분비되는 테스토스테론에 의존적이지만, 테스토스테론으로부터 유도되는 dihydroxytestosterone(DHT)와 에스트로겐도 중요한 역할을 한다. 본 연구에서는 EDS 주사 후 7주까지 부정소에서의 스테로이드 호르몬 수용체, cyctochrome P450aromatase(P450arom)와 $5{\alpha}$-reductase의 유전자 발현 양상을 조사하였다. 성숙한 수컷 흰쥐($350{\sim}400\;g$)에 EDS를 1회 복강 주사하고(75 mg/kg i.p.) 주사 후 0, 1, 2, 3, 4, 5, 6, 7주가 경과한 날에 희생하였다. 표적 유전자들의 전사 활성은 반 정량적 역전사 중합효소 반응법(semi-quantitative RT-PCRs)으로 측정하였다. Estrogen receptor alpha($ER{\alpha}$) 전사 수준은 EDS 실험군에서 대조군에 비해 주사 1주후에 유의하게 상승했으나(P<0.01) 2주 후부터는 대조군과 유의적인 차이를 보이지 않았다. Estrogen receptor beta($ER{\beta}$)의 전사 수준은 주사 1주후 EDS 실험군에서 대조군에 비해 유의하게 증가했다가(P<0.05), 2주와 3주에는 감소하였고(P<0.05와 P<0.01), 4주와 6주까지는 변동폭을 보이다가 7주 후에는 대조군에 비해 증가하였다(P<0.05). Androgen receptor(AR) 전사 수준은 주사 2주 후에 유의하게 증가하다가(P<0.01) 3주 후부터는 대조군 수준으로 회복하였다. 반면, P450arom는 주사 1주 후부터 3주까지 급격하게 감소했다가(P<0.01 1주와 2주; P<0.05 3주), 4주에 대조군 수준으로 회복하였다. $5{\alpha}$-reductase type 2($5{\alpha}$-RT2)의 mRNA 수준은 4주 후 유의하게 증가했다가(P<0.01), 이후 대조군 수준으로 회복하였다. 본 연구는 EDS 주사가 성 스테로이드 호르몬 수용체들과 안드로겐 전환 효소들의 전사 활성에 가역적인 변화를 유도함을 보여준 것이다. EDS 주사 모델은 부정소의 생리 조절 기작을 이해하는데 유용할 것으로 사료된다.