• The Korean Journal of Nuclear Medicine
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• v.15 no.2
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• pp.53-57
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• 1981

The estrogen and progesterone receptors which are bound to the cytoplasmic protein of cancer cells were measured in 20 patients with the early breast cancer by means of radioimmunoassay using charcoal. 1. The Patients with estrogen receptor positive were 13 (65%) of 20 cases and with progestrone receptor positive were 7 cases (35%) in the early breast cancer. 2. Coexistence of estrogen and progesterone receptor positive was noted in 7 cases (35%). The cases of estrogen receptor positive and progesterone receptor negative were 6 cases (33.3%), while there were no cases of estrogen receptor negative with progestrone receptor positive. 3. Coincidence of estrogen and progesterone negative was notied in 7 cases(35%). Conclusively, it is considered that the measurement of estrogen and progesterone receptors has relevance as predictive value, in the response to hormonal manipulations and chemotherapy for breast cancer patients.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.70-70
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• 2003

Estrogen receptor is a ligand-activated transcription factor. Its action depends on the receptor, its ligand, and its coactivator proteins. As a consequence, the concentration of the receptor is a major component that governs the magnitude of the estrogen response. Despite the extensive knowledge on mechanism of estrogen receptor action, regulation of estrogen receptor itself is not very well understood. Estrogen receptor is known to be downregulated under hypoxia leading to inhibition of estrogen receptor mediated transcription activation. We have studied mechanism of loss of estrogen responsiveness under hypoxia. We found that Hif-l${\alpha}$, a major transcription factor regulating hypoxic response, inhibited transcription of estrogen response element driven luciferase gene by expression of HIF-l${\alpha}$/vp16 construct designed to contain transcription activity under normoxia. This loss of estrogen responsiveness appears to be the result of ER${\alpha}$ downregulation. ER${\alpha}$was downregulated at the levels of ligand-biding and protein within l2-24h, and the response was blocked by the proteasome inhibitor MG132, protein synthesis inhibitor cyclohexamide, and tyrosine kinase inhibitor Genistein. These results demonstrate that Hif-l${\alpha}$ downregulates ER${\alpha}$ by proteasome dependent pathway.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.12
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• pp.1716-1721
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• 2003

Steroid hormones and their receptors play an important role in reproductive process. Estrogen is intimately involved with pregnancy and its function is mediated through the estrogen receptor which has been chosen as a candidate gene to study litter size in pigs. In this study, we report that two estrogen receptor variants, designated pER-1 and pER-2 were co-expressed in the uteri of normal cycling Lan-Yu pig (Sus vittatus; a small-ear miniature in Taiwan) with the pER-1 expression level appeared to be several times higher than that of pER-2. These receptor variants were isolated using reverse transcription-PCR from the pig uteri and their sequences were determined. The pER-1 and pER-2 sequences, which are homologous to those found in other mammalian estrogen receptors, encode putative proteins consisting of 574 and 486 amino acids, respectively. A deletion in exon I was identified in both sequences, with deletion lengths of 63 bp in pER-1 and 327 bp in pER-2. The deletion in pER-1 is internal to that in pER-2 and both deletions resulted in a truncation of the B domain, which confers the transactivating activity of estrogen receptor protein. This result describes the existence of estrogen receptor variants with a deletion in exon I and implies the possibility that physiological functioning of an estrogen receptor may not require the presence of an intact B domain.

• Archives of Pharmacal Research
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• v.27 no.5
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• pp.554-561
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• 2004

Trichostatin A, an antifungal antibiotics, and HC-toxin are potent and specific inhibitors of histone deacetylase activity. Histone deacetylase inhibitors are new class of chemotherapeutic drugs able to induce tumor cell apoptosis and/or cell cycle arrest. In this study, the antiproliferative activities of trichostatin A and HC-toxin were compared between estrogen receptor positive human breast cancer cell MCF-7 and estrogen receptor negative human breast cancer cell MDA-MB-468. Trichostatin A and HC-toxin showed potent antiproliferative activity in both MCF-7 and MDA-MB-468 cells. In MCF-7 cells that contain high level estrogen receptor, trichostatin A and HC-toxin brought about three-times more potent cell growth inhibitory effect than estrogen receptor negative MDA-MB-468 cells. Both trichostatin A and HC-toxin showed cell cycle arrest at G$_2$/M phases of MCF-7 and MDA-MB-468 cells in a dose- and time- depen- dent manner. Trichostatin A and HC-toxin also induced apoptosis from MCF-7 and MDA-MB-468 cells in a dose- and time-dependent manner. Results of this study suggested that antipro-liferative effects of trichostatin A and HC-toxin might be involved in estrogen receptor signaling pathway, but cell cycle arrest and apoptosis of trichostatin A and HC-toxin might not be involved in estrogen receptor system of human breast cancer cells.

• Journal of Gastric Cancer
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• v.13 no.3
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• pp.172-178
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• 2013

Purpose: The aims of this study were as follow: 1) to de scribe the expression status of estrogen receptor-${\alpha}$ and -${\beta}$ mRNAs in five gastric carcinoma cell lines; 2) to evaluate in vitro the effects of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of the cell lines. Materials and Methods: Detection of estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNA in five human gastric cancer cell lines (AGS, KATO III, MKN28, MKN45 and MKN74) was made by the reverse transcription-polymerase chain reaction system. To evaluate the effect of $17{\beta}$-estradiol and estrogen receptor antagonists on the proliferation of gastric cancer cell line, the cell lines which expressed both es trogen receptors were chosen and treated with $17{\beta}$-estradiol and estrogen receptor antagonists (methyl-piperidino-pyrazole and pyrazolo [1,5-a] pyrimidine). Cell proliferation was assessed with the methylthiazol tetrazolium test. Results: Estrogen receptor-${\alpha}$ and estrogen receptor-${\beta}$ mRNAs were expressed in three (KATO III, MKN28 and MKN45) and all of the five gastric cancer cell lines, respectively. At higher concentrations, $17{\beta}$-estradiol inhibited cell growth of MKN28, MKN45 and KATO III cell lines. Neither estrogen receptor-${\alpha}$ nor estrogen receptor-${\beta}$ antagonist blocked the anti-proliferative effect of $17{\beta}$-estradiol. Conclusions: Our results indicate that estrogen receptor-${\beta}$ mRNAs are preferentially expressed in gastric cancers and also imply that hormone therapy rather than estrogen receptor blockers may be a useful strategy for the treatment of estrogen receptor-${\beta}$ positive gastric cancer. Its therapeutic significance in gastric cancer are, however, limited until more evidence of the roles of estrogen receptors in the gastric cancer are accumulated.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.228.2-229
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• 2003

Estrogen Receptor is a ligand-activated transcription factor. The concentration of the receptor is a major component that regulates expression of estrogen-responsive genes. We have studied mechanism of estrogen receptor alpha (ER${\alpha}$) downregulation by HIF-1 using HIF-1${\alpha}$/VP16 constructs. ER${\alpha}$ is known to be downregulated under hypoxic condition. Transcriptional response under hypoxia is mediated through Hypoxia-inducible factor-1 (HIF-1), a transcription factor that is usullaly degraded but stabilized under hypoxia. (omitted)

• Applied Microscopy
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• v.46 no.4
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• pp.193-200
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• 2016

Male reproductive organs are strongly affected by estrogen signaling mediated via the estrogen receptor. In this study, propyl pyrazole triol (PPT), an estrogen receptor alpha agonist, was subcutaneously injected in adult male mice every 2 days for a total duration of 8, 16, or 24 days. Histological changes in the reproductive organs, including the testes, efferent ductules, and epididymides, were observed. The weight of the reproductive organs decreased in the PPT group. In addition, the diameter of the seminiferous tubules decreased in the PPT group compared with the control group. The epithelial cell height decreased in the initial segment of the epididymis, whereas the luminal diameter increased in the efferent ductules of the PPT group. PPT induced irregular morphology of stereocilia in the luminal region of the initial segment. Therefore, PPT treatment at high concentrations had inhibitory effects in the reproductive organs of adult male mice. These findings suggest that short-term treatment with estrogen receptor agonist causes histological changes in the testes, efferent ductules, and epididymis, which are similar to those caused by estrogen receptor antagonist treatment. Therefore, the estrogen receptor may have functional roles in male reproductive organs, implying that treatment with an estrogen receptor agonist can affect male fertility.

• Development and Reproduction
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• v.11 no.3
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• pp.179-185
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• 2007

The estrogens and estrogenic endocrine disrupting chemicals(EDCs) function through a steroid nuclear receptor-mediated process and subsequently regulate the transcription of mRNA for a number of target proteins. The estrogen receptor-related receptors(ERRs), which are structurally similar to estrogen receptors, are members of orphan nuclear receptor in the nuclear receptor superfamily and their functions are known to be involved in the formation of extra-embryonic ectoderm. To investigate effects of EDCs on early embryogenesis and ERR gene expression in marine invertebrates, we examined morphological changes and the mRNA expression of $ERR{\beta}$ like 1 in sea urchin Strongylocentrotus nudus exposed to estradiol-$17{\beta}(E_2)$ or nonylphenol(NP). The $E_2$ and NP-exposed embryos showed a delayed development compared to control embryos. Furthermore, they showed abnormal embryonic developments at late stages, i.e., blastular, gastrula and plutei stages. The mRNA level of $ERR{\beta}$ like 1 at the gastrula stage was significantly lower in $E_2$ and NP-exposed embryos than those of control group. These results suggest that NP and $E_2$ are potent chemicals causing abnormal embryonic development of S. nudus through at least in part down-regulated $ERR{\beta}$ like 1.

• Animal cells and systems
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• v.13 no.2
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• pp.205-212
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• 2009

Known as a female hormone, estrogen, performs important functions, and the activities of the hormone are mediated via the estrogen receptor. The principal objective of the present study was to assess the effects of a estrogen receptor agonist in male reproductive organs. In this study, the estrogen receptor alpha agonist, PPT, was injected subcutaneously into adult male mice. The effects of PPT on the murine reproductive system were histologically assessed at 3,5, and 8 weeks after treatment. In the treatment group, reductions were observed in the weight of the body, testis and epididymis. Microscopic examination revealed a reduction in seminiferous tubular diameter in the testis, and epithelial cell height in the epididymis during the experiment. 8 weeks after treatment, spermatogenesis was not detected, nor was the lumen of the seminiferous tubules. In the fertility test, 1 week after PPT injection, the fertilizing ability of males was decreased, and on the 2nd and 3rd weeks, complete infertility was observed. In conclusion, the injection of high concentrations of PPT into adult males induced physiological changes, including infertility, and also induced morphological changes, including a reduction in the height of epithelial cells within the reproductive system.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.11.1-11.9
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• 2018

Estrogen has diverse effects on cardiovascular function, including regulation of the contractile response to vasoactive substances such as serotonin. The serotonin system recently emerged as an important player in the regulation of vascular tone in humans. However, hyperreactivity to serotonin appears to be a critical factor for the pathophysiology of hypertension. In this study, we examined the modulatory mechanisms of estrogen in serotonin-induced vasoconstriction by using a combinatory approach of isometric tension measurements, molecular biology, and patch-clamp techniques. $17{\beta}$-Estradiol (E2) elicited a significant and concentration-dependent relaxation of serotonin-induced contraction in deendothelialized aortic strips isolated from male rats. E2 triggered a relaxation of serotonin-induced contraction even in the presence of tamoxifen, an estrogen receptor antagonist, suggesting that E2-induced changes are not mediated by estrogen receptor. Patch-clamp studies in rat arterial myocytes showed that E2 prevented Kv channel inhibition induced by serotonin. Serotonin increased Src activation in arterial smooth muscle required for contraction, which was significantly inhibited by E2. The estrogen receptor-independent inhibition of Src by E2 was confirmed in HEK293T cells that do not express estrogen receptor. Taken together, these results suggest that estrogen exerts vasodilatory effects on serotonin-precontracted arteries via Src, implying a critical role for estrogen in the prevention of vascular hyperreactivity to serotonin.