• Bulletin of the Korean Chemical Society
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• v.29 no.6
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• pp.1107-1114
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• 2008

It is important to identify selective ligands for the estrogen receptor subtypes ER$\alpha$ or ER$\beta$ to evaluate them as pharmaceutical targets in breast cancer. To develop ER$\beta$-selective ligands as PET imaging agents, a series of aryl indazole estrogen analogues substituted at the C3 position with fluoroethyl and fluoropropyl groups were synthesized and evaluated for their relative binding affinities and selectivities for ER$\alpha$ vs ER$\beta$. The fluoroethylated indazole estrogen (FEIE, 1i) and fluoropropylated indazole estrogen (FPIE, 1h) showed 41- fold and 17-fold ER$\beta$/ER$\alpha$ selectivity, respectively. However, their binding affinities to ER$\alpha$ and ER$\beta$ were very low.

• Korean Journal of Animal Reproduction
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• v.23 no.4
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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.

• The Plant Pathology Journal
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• v.27 no.4
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• pp.349-353
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• 2011

The ascomycete fungus Fusarium graminearum is an important plant pathogen responsible for Fusarium head blight in small grains and ear rot on maize. This fungus also produces the estrogenic metabolite, zearalenone (ZEA) that causes estrogenic disorders in humans and animals. Previously, we developed a conditional gene expression system for this fungus using a ZEA-inducible promoter (Pzear). In the present study, four other estrogenic compounds, including ${\beta}$-estradiol, estriol, estrone, and secoisolariciresinol, were screened as possible substitutes for ZEA in this system. Among them, ${\beta}$-estradiol was able to successfully induce the expression of a gene controlled by Pzear, while estrone was only able to partially induce its expression but the other two compounds were not effective. In combination, these results demonstrate that ${\beta}$-estradiol can replace ZEA in this conditional gene expression system, thereby eliminating the need to use the more expensive reagent, ZEA, and facilitating high-throughput functional analyses of F. graminearum in future studies.

• Journal of Nutrition and Health
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• v.34 no.8
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• pp.905-911
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• 2001

Phytoestrogens, especially soy-derived isoflavones, are receiving great scrutiny as a food supplement for preventing hormone dependent diseases such as cardiovascular diseases, cancer, and osteoporosis. These beneficial effects of phytoestrogens are caused by functioning as partial agonists or antagonists of estrogens. In contrast to the common usage of soy bean, Yak-kong(Rhynchosia Molubilis ; ) has been used as supplements of estrogen fir preventing postmenopausal osteoporosis in Oriental medicine. To investigate estrogenic effects of Yak-kong and soy bean on the proliferation of MG-63 osteoblastic cells, each bean was extracted with 70% methanol and dried by freeze-drying. Yak-kong treatment of MG-63 cells resulted in an increase of cell proliferation to a maximum of 76% compared to 68% of soy bean treatment. Treatment of MG-63 cells with Yak-kong extract also resulted in an increase of transactivation of an ERE(estrogen response element)-luciferase reporter plasmid and IGF-I expression selectively. Despite increased effects of both bean treatments on the expression of estrogen receptor $\alpha$(ER$\alpha$) and $\beta$(ER$\beta$), soy bean treatment decreased transactivation of an ERE-luciferase reporter plasmid and did not further enhance IGF-I expression. Together, our data demonstrates that the greater estrogenic response of Yak-kong extract for MG-63 cell proliferation is mediated by ER derived transactivation of ERE and selective induction of IGF-I expression.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.3
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• pp.123-129
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• 2006

In several experimental models, estrogens protect neurons against ischemic insults. However, the recent clinical studies of hormone replacement showed negative results to prevent stroke. Therefore, optimal models to study estrogen replacement for neuroprotection are needed before its clinical ap-plication. Organotypic hippocampal slice under oxygen-glucose deprivation (OGD) has been established as a model of cerebral ischemia and has advantages to study drug effects. We investigated whether estrogen protected CAI neurons and affected activation of Akt (pAkt) in CAI region under OGD. Thus, rat hippocampal slices on day 7 of culture were treated with $17-{\beta}$ estradiol (E, 1 nM) for 7 days before 30 min OGD, and cell death of CAI neurons was quantified by propidium iodide (PI) staining and expression of pAkt was studied by Western blot and immunofluorescence. PI intensity in slices treated with E was significantly reduced 72 hour after OGD compared to that of non-treated slices (p < 0.05). E pretreatment also increased the expression of pAkt 72 hour after OGD compared to that of no treatment (p<0.01). These data suggest that estrogen pretreatment may rescue neurons from ischemic insults through the activation of Akt and also indicate that our model would be a useful alternative method to study the mechanisms and effects of estrogen replacement treatment for neuroprotection.

• Clinical and Experimental Reproductive Medicine
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• v.42 no.2
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• pp.72-76
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• 2015

$17{\alpha}$-hydroxylase and 17,20-lyase are enzymes encoded by the CYP17A1 gene and are required for the synthesis of sex steroids and cortisol. In $17{\alpha}$-hydroxylase deficiency, there are low blood levels of estrogens, androgens, and cortisol, and resultant compensatory increases in adrenocorticotrophic hormone that stimulate the production of 11-deoxycorticosterone and corticosterone. In turn, the excessive levels of mineralocorticoids lead to volume expansion and hypertension. Females with $17{\alpha}$-hydroxylase deficiency are characterized by primary amenorrhea and delayed puberty, with accompanying hypertension. Affected males usually have female external genitalia, a blind vagina, and intra-abdominal testes. The treatment of this disorder is centered on glucocorticoid and sex steroid replacement. In patients with $17{\alpha}$-hydroxylase deficiency who are being raised as females, estrogen should be supplemented, while genetically female patients with a uterus should also receive progesterone supplementation. Here, we report a case of a 21-year-old female with $17{\alpha}$-hydroxylase deficiency who had received inadequate treatment for a prolonged period of time. We also include a brief review of the recent literature on this disorder.

• Clinical and Experimental Reproductive Medicine
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• v.41 no.3
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• pp.108-114
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• 2014

Male factors account for 20%-50% of cases of infertility and in 25% of cases, the etiology of male infertility is unknown. Effective treatments are well-established for hypogonadotropic hypogonadism, male accessory gland infection, retrograde ejaculation, and positive antisperm antibody. However, the appropriate treatment for idiopathic male infertility is unclear. Empirical medical treatment (EMT) has been used in men with idiopathic infertility and can be divided into two categories based on the mode of action: hormonal treatment and antioxidant supplementation. Hormonal medications consist of gonadotropins, androgens, estrogen receptor blockers, and aromatase inhibitors. Antioxidants such as vitamins, zinc, and carnitines have also been widely used to reduce oxidative stress-induced spermatozoa damage. Although scientifically acceptable evidence of EMT is limited because of the lack of large, randomized, controlled studies, recent systematic reviews with meta-analyses have shown that the administration of gonadotropins, anti-estrogens, and oral antioxidants results in a significant increase in the live birth rate compared with control treatments. Therefore, all physicians who treat infertility should bear in mind that EMT can improve semen parameters and subsequent fertility potential through natural intercourse.

• Preventive Nutrition and Food Science
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• v.11 no.4
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• pp.268-272
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• 2006

Cimicifugae Rhizoma (CR) belongs to the Ranunculaceae family, which has been traditionally used to treat climacteric complaints, antipyretics and diaphoresis as an alternative medicine for estrogen hormone replacement therapy with estrogens. Recently, it has been reported that different extract fractions of CR have various effects such as anti-allergic, anti-inflammatory and anti-proliferative activities. The current study investigated the immunomodulatory effects of Cimicifugae Rhizoma water extracts (CRE) in the macrophage-like cell line, Raw 264.7. Our results showed that CRE ($1\sim50\;{\mu}g/mL$) stimulated tumoricidal activity and NO production, whereas phagocytic activity was inhibited at the same concentrations. Additionally, iNOS mRNA expression was significantly increased in Raw 264.7 exposed to CRE as demonstrated by RT-PCR. These results indicate that the tumoricidal activity induced by CRE may be mediated by the production of NO and these activities may be useful for the treatment of diseases such as cancer.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.162-162
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• 2002

There has been many findings of natural, environmental or manufactered nonsteroidal substances shown to have estrogenic activity. Since estrogens affect reproduction and cellular development to cause disease in people or animals, chronic exposure may have a major impact on health.(omitted)

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.321-328
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• 2017

Steroid sulfatase (STS) is an enzyme responsible for the hydrolysis of aryl and alkyl sulfates. STS plays a pivotal role in the regulation of estrogens and androgens that promote the growth of hormone-dependent tumors, such as those of breast or prostate cancer. However, the molecular function of STS in tumor growth is still not clear. To elucidate the role of STS in cancer cell proliferation, we investigated whether STS is able to regulate the integrin signaling pathway. We found that overexpression of STS in HeLa cells increases the protein and mRNA levels of integrin ${\beta}1$ and fibronectin, a ligand of integrin ${\alpha}5{\beta}1$. Dehydroepiandrosterone (DHEA), one of the main metabolites of STS, also increases mRNA and protein expression of integrin ${\beta}1$ and fibronectin. Further, STS expression and DHEA treatment enhanced phosphorylation of focal adhesion kinase (FAK) at the Tyr 925 residue. Moreover, increased phosphorylation of ERK at Thr 202 and Tyr 204 residues by STS indicates that STS activates the MAPK/ERK pathway. In conclusion, these results suggest that STS expression and DHEA treatment may enhance MAPK/ERK signaling through up-regulation of integrin ${\beta}1$ and activation of FAK.