• 대한의생명과학회지
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• 제15권3호
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• pp.171-177
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• 2009

This study investigated whether increased adiposity is prevented by estrogen replacement in female ovariectomized (OVX) C57BL/6J mice, an animal model of human menopause and whether these metabolic changes reflect the inhibitory action of estrogen on peroxisome proliferator-activated receptor $\gamma$ ($PPAR{\gamma}$)-regulated gene expression. Treatment of $17{\beta}$-estradiol for the last one week of the experiment decreased high fat diet-induced body weight gain and white adipose tissue mass compared to OVX control mice. Histological analysis showed that administration of $17{\beta}$-estradiol to mice decreased the size of adipocytes in parametrial adipose tissue versus OVX control mice. In addition, $17{\beta}$-estradiol reduced the adipose expression of $PPAR{\gamma}$ as well as $PPAR{\gamma}$ target genes such as adipocyte fatty acid binding protein and tumor necrosis factor $\alpha$. These results suggest that $17{\beta}$-estradiol may inhibit adiposity through reducing the $PPAR{\gamma}$ activities in female OVX mice.

• The Korean Journal of Physiology and Pharmacology
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• 제26권2호
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• pp.113-123
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• 2022

Diarylpropionitrile (DPN), a selective agonist for estrogen receptor β (ERβ), has been reported to regulate various hormonal responses through activation of ERβ in tissues including the mammary gland and brain. However, the effect of DPN on melanogenesis independent of ERβ has not been studied. The aim of this study is to examine the possibility of anti-melanogenic effect of DPN and its underlying mechanism. Melanin contents and cellular tyrosinase activity assay indicated that DPN inhibited melanin biosynthesis in alpha-melanocyte stimulating hormone-stimulated B16F10 melanoma cell line. However, DPN had no direct influence on in vitro tyrosinase catalytic activity. On the other hand, 17β-estradiol had no effect on inhibition of melanogenesis, suggesting that the DPN-mediated suppression of melanin production was not related with estrogen signaling pathway. Immunoblotting analysis showed that DPN down-regulated the expression of microphthalmia-associated transcription factor (MITF), a central transcription factor of melanogenesis and its down-stream genes including tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. Also, DPN attenuated the phosphorylation of protein kinase A (PKA) and cAMP-response element-binding protein (CREB). Additionally, DPN suppressed the melanin synthesis in UVB-irradiated HaCaT conditioned media culture system suggesting that DPN has potential as an anti-melanogenic activity in physiological conditions. Collectively, our data show that DPN inhibits melanogenesis via downregulation of PKA/CREB/MITF signaling pathway.

• 생명과학회지
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• 제24권10호
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• pp.1070-1077
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• 2014

에스트로겐 수용체 알파에 높은 친화성을 갖고 있는 수용체 촉진제인 propyl pyrazole triol (PPT)을 성체 수컷 생쥐에 이틀 간격으로 8일, 16일, 24일 동안 피하주사방법으로 투여하였다. 현미경으로 부속 생식샘인 전립샘과 정낭, 그리고 간의 조직학적 변화를 관찰하였다. 대조군에 비해, PPT 투여군의 체중과 생식샘의 무게는 감소하였지만 간의 무게는 오히려 증가하였다. PPT 투여군에서 전립샘과 정낭의 내강 면적이 축소되었다. PPT 투여군 전립샘의 상피세포 높이는 대조군에 비해 증가하였다. 정낭의 경우, 상피세포의 핵 위쪽 세포질에 있는 분비 소포가 대조군에서는 나타났지만, PPT 군에서는 잘 관찰되지 않았다. 대조군에 비해 PPT 투여군 간의 굴모양혈관 직경이 투여횟수에 누적적으로 147.0%, 198.7%, 223.3% 의 비율로 증가되었다. 이런 결과는 PPT 투여로 인해 생식기관과 간의 조직 구조가 영향을 받으며, 그 조직학적 변화는 투여회수에 따라 더 심하게 나타났다. 결론적으로 이틀에 한번씩 투여한 PPT에 의해서 생식력 변화와 관련 있는 생식기관의 상피세포 높이 변화가 일어났고, 내강의 크기가 위축되었다. 간의 굴모양혈관 직경이 급격하게 확대되었으며, 이 결과는 간의 무게 증가로 이어졌다.

• Journal of Microbiology and Biotechnology
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• 제14권6호
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• pp.1286-1294
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• 2004

In a previous study by the current authors, hepatocellular carcinoma (HCC) was determined to be epidemiologically sex-dependent, and the incidence and multiplicity of HCC found to decrease in estradiol-3 benzoate (EB)-treated F344 rats. Therefore, to ascertain the anticancer mechanism of EB, a commercially available cDNA microarray, with a total of 14,815 cDNA rat gene clones, was used to determine the differentially expressed genes in nontreated livers, EB-treated livers, and diethynitrosolamine (DEN)-induced HCC. In the sequenced experiment, a total of 85 genes were differentially expressed at either two or more times the rate of the normal expression, where 33 genes were downregulated by EB, and 52 genes upregulated. Candidate genes were selected according to significant changes observed in the mRNA expression in the EB-treated livers compared with the nontreated livers, then these genes were filtered according to their different expression patterns in the DEN-induced tumors compared to the estrogen-treated livers. To confirm the microarray data, a real-time PCR analysis was performed for ten selected genes: the H-ras revertant protein 107 (H­rev107), insulin-like growth factor binding protein (lOFBP), parathyroid hormone receptor (PI'HR), SH3 domain binding protein (SH3BP), metallothionein, src-suppressed C-kinase substrate (SSeCK) gene, phosphodiesterase I, CD44, epithelial membrane protein 3 (EMP3), and estrogen receptor a (ERa). The SSeCK and phosphodiesterase I genes were both upregulated in the DEN-induced hepatocarcinomas, yet their possible carcinogenic functions remain unknown. Meanwhile, the other genes were downregulated, including the genes related to growth regulation (IOFBP, H-revI07, ER$\alpha$), adipogenesis inhibition (PTHR), and tumor suppression (metallothionein).

• Molecules and Cells
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• 제45권6호
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• pp.425-434
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• 2022

The post-translational modification (e.g., phosphorylation) of estrogen receptor α (ERα) plays a role in controlling the expression and subcellular localization of ERα as well as its sensitivity to hormone response. Here, we show that ERα is also modified by UFM1 and this modification (ufmylation) plays a crucial role in promoting the stability and transactivity of ERα, which in turn promotes breast cancer development. The elevation of ufmylation via the knockdown of UFSP2 (the UFM1-deconjugating enzyme in humans) dramatically increases ERα stability by inhibiting ubiquitination. In contrast, ERα stability is decreased by the prevention of ufmylation via the silencing of UBA5 (the UFM1-activating E1 enzyme). Lys171 and Lys180 of ERα were identified as the major UFM1 acceptor sites, and the replacement of both Lys residues by Arg (2KR mutation) markedly reduced ERα stability. Moreover, the 2KR mutation abrogated the 17β-estradiol-induced transactivity of ERα and the expression of its downstream target genes, including pS2, cyclin D1, and c-Myc; this indicates that ERα ufmylation is required for its transactivation function. In addition, the 2KR mutation prevented anchorage-independent colony formation by MCF7 cells. Most notably, the expression of UFM1 and its conjugating machinery (i.e., UBA5, UFC1, UFL1, and UFBP1) were dramatically upregulated in ERα-positive breast cancer cell lines and tissues. Collectively, these findings implicate a critical role attributed to ERα ufmylation in breast cancer development by ameliorating its stability and transactivity.

• 한국식품과학회지
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• 제51권4호
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• pp.361-368
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• 2019

황칠추출분말은 여성호르몬인 에스트로겐과 구조적 유사성을 가진 루틴을 다량 함유하고 있다(황칠추출분말 1g당 11.19 mg의 루틴 함유). 루틴은 식물성 여성호르몬이라고 불리는 플라보노이드 성분의 일종으로, 에스트로겐 수용체를 통한 신호전달을 증가시킨다. 특히 $ER-{\alpha}$로부터 세포내로 전달되는 MAPK/ERK 신호 전달 경로를 활성화시킴으로써, 갱년기의 대표적인 만성증상들을 개선할 수 있는 가능성이 있다고 여겨진다. 본 연구는 루틴이 다량 함유된 황칠추출분말을 폐경의 유도를 위해 난소를 절제한 쥐에 투여하여 여성갱년기 증상의 개선에 미치는 영향을 평가하였다. 그 결과 골교체율 관련 지표로서 폐경기 여성에서 높다고 알려진 오스테오칼신이 감소하는 경향성을 나타냈고, CTX는 유의적인 감소를 나타냈을 뿐만 아니라, 에스트로겐 수용체의 활성화를 증가시키는 경향성을 나타냈다. 이를 통해, 황칠추출분말은 골다공증의 예방 및 개선 효과를 나타내는 갱년기 여성 건강에 도움을 줄 수 있는 기능성 원료로서의 가능성을 보여준다.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 춘계학술대회
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• pp.195-195
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• 2003

It is well known that diesel exhaust particulate matter contains mutagenic PAHs, such as benzo[${\alpha}$]pyrene, benz[${\alpha}$]anthracene, chrysene, etc. Therefore it is suspected that these chemicals act on estrogen receptor and reveal endocrine-disrupting effects. Recent attention has focused on causative chemicals of endocrine-disrupting effects. We examined the estrogenic activity of respirable diesel exhaust particulate matter derived from diesel powered vehicle. PM2.5 diesel exhaust of vehicle was collected using a high volume sampler equipped with a cascade impactor. Diesel exhaust samples were fractionated according to EPA methods. The presence of estrogenic and antiestrogenic chemicals in PM 2.5 diesel exhaust was determined using E-screen assay. To quantitatively assess the estrogenic and antiestrogenic activities in diesel exhaust particulate matter, estradiol equivalent concentration (bio-EEQ) was calculated by comparing the concentration response curve of the sample with those of the estrogen calibration curve. Weak estrogenic activities and strong antiestrogenic activities were detected in the crude extract and moderately polar fractions. Higher antiestrogenic potency was observed with higher EROD activities in aliphatic and aromatic compounds fraction. In conclusion, estrogenic/antiestrogenic-like activities were present in diesel exhaust particulate matter. However, the health consequences of this observation was unknown, the presence of these activities may contribute to and exacerbate adverse health effect evoked by diesel exhaust particulate matter.

• 한국가축번식학회지
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• 제23권4호
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• pp.365-369
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• 1999

Interferon tau (IFN$\tau$), the pregnancy recognition signal in ruminants, suppresses transcription of the estrogen receptor (ER) gene in the endometrial luminal (LE) and superficial glandular epithelium (sGE) to prevent oxytocin receptor (OTR) expression and pulsatile release of luteolytic prostaglandin $F_{2{\alpha}}$ (PGF), Interferon regulatory factors one (IRF-l) and two (IRF-2) are transcription factors induced by IFN$\tau$ that activate and silence gene expression, respectively. Available results suggest that IFN$\tau$ acts directly on LE and sGE during pregnancy to induce sequentially IRF-l and then IRF-2 gene expression to silence transcription of ER and OTR genes, block the luteolytic mechanism to maintenance a functional corpus luteum (CL) and, signal maternal recognition of pregnancy. The theory for maternal recognition of pregnancy in pigs is that the uterine endometrium of cyclic gilts secretes PGF in an endocrine direction, toward the uterine vasculature for transport to the CL to exert its luteolytic effect. However, in pregnant pigs, estrogens secreted by the conceptuses are responsible, perhaps in concert with effects of prolactin and calcium, for exocrine secretion of PGF into the uterine lumen where it is sequestered to exert biological effects and / or be metabolized to prevent luteolysis.

• Toxicological Research
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• 제31권4호
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• pp.331-337
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• 2015

Synthetic pyrethroids (SPs) are the most common pesticides which are recently used for indoor pest control. The widespread use of SPs has resulted in the increased exposure to wild animals and humans. Recently, some SPs are suspected as endocrine disrupting chemicals (EDCs) and have been assessed for their potential estrogenicity by adopting various analyzing assays. In this study, we examined the estrogenic effects of lambda-cyhalothrin (LC) and cypermethrin (CP), the most commonly used pesticides in Korea, using BG-1 ovarian cancer cells expressing estrogen receptors (ERs). To evaluate the estrogenic activities of two SPs, LC and CP, we employed MTT assay and reverse-transcription polymerase chain reaction (RT-PCR) in LC or CP treated BG-1 ovarian cancer cells. In MTT assay, LC ($10^{-6}M$) and CP ($10^{-5}M$) significantly induced the growth of BG-1 cancer cells. LC or CP-induced cell growth was antagonized by addition of ICI 182,720 ($10^{-8}M$), an ER antagonist, suggesting that this effect appears to be mediated by an ER-dependent manner. Moreover, RT-PCR results showed that transcriptional level of cyclin D1, a cell cycle-regulating gene, was significantly up-regulated by LC and CP, while these effects were reversed by co-treatment of ICI 182,780. However, p21, a cyclin D-ckd-4 inhibitor gene, was not altered by LC or CP. Moreover, $ER{\alpha}$ expression was not significantly changed by LC and CP, while down-regulated by E2. Finally, in xenografted mouse model transplanted with human BG-1 ovarian cancer cells, E2 significantly increased the tumor volume compare to a negative control, but LC did not. Taken together, these results suggest that LC and CP may possess estrogenic potentials by stimulating the growth of BG-1 ovarian cancer cells via partially ER signaling pathway associated with cell cycle as did E2, but this estrogenic effect was not found in in vivo mouse model.

• Toxicological Research
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• 제20권3호
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• pp.251-261
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• 2004

A large number of chemical pollutants including phthalates, alkylphenolic compounds and organochlorine pesticides have the ability to disrupt endocrine function in animals, and alter cog-nitive function. Because hormone mediated events play an important role in central nervous system development and function, the changes in cognitive function seem to be mediated by the endocrine-like action of these chemicals. The present study therefore was designed to investigate effect of bisphenol A (BPA), an endocrine disrupting chemical on neuro-behavial patterns, and expression of estrogen receptors and tyrosine hydroxylase, a limiting enzyme of dopamine synthesis pathway. BPA was treated orally for 3 weeks into 3 week old mice, and then the neuro-behavial patterns (stereo-type behaviors such as jumping rearing and forepaw tremor, climbing behavior, tail flick, rotarod and locomotor activity), and the expression of estrogen receptors and tyrosine hydroxylase were deter-mined every 3 week for 9 weeks. During the treatment of BPA, the food uptake and body weight increase were not significantly changed. BPA resulted in the increased stereotype behaviors (jump-ing, rearing and forepaw tremor) 6 or 9 weeks after treatment. The time response to tail flick and locomotor activity were decreased by the treatment of BPA, whereas the time for rotarod was increased by the treatment of BPA. The expression of estrogen receptor alpha and beta was increased in the brain and pituitary gland. Maximum expression was found in the brain after 9 week of 100 mg/kg BPA treatment and in the pituitary gland after 6 week of 100 mg/kg BPA treatment. Tyrosine hydroxylase was increased in dose and time dependent manners in the brain but no change was found in the pituitary gland. The present data show that exposure of BPA in the young mice could alter expression of estrogen receptors and dopamine synthesis pathway, thereby modulate neuro-behavial patterns (increase of stereotype behaviors but decrease locomotor activity).