• Molecules and Cells
• /
• 제25권2호
• /
• pp.265-271
• /
• 2008

Single nucleotide polymorphisms (SNPs) are the most common form of human genetic variation. Non-synonymous SNPs (nsSNPs) change an amino acid. Organic anion transporters (OATs) play an important role in eliminating or reabsorbing endogenous and exogenous organic anionic compounds. Among OATs, hOAT4 mediates high affinity transport of estrone sulfate and dehydroepiandrosterone sulfate. The rapid bone loss that occurs in post-menopausal women is mainly due to a net decrease of estrogen. In the present study we searched for SNPs within the exon regions of hOAT4 in Korean women osteoporosis patients. Fifty healthy subjects and 50 subjects with osteoporosis were screened for genetic polymorphism in the coding region of SLC22A11 (hOAT4) using GC-clamp PCR and denaturing gradient gel electrophoresis (DGGE). We found three SNPs in the hOAT4 gene. Two were in the osteoporosis group (C483A and G832A) and one in the normal group (C847T). One of the SNPs, G832A, is an nsSNP that changes the $278^{th}$ amino acid from glutamic acid to lysine (E278K). Uptake of [$3^H$] estrone sulfate by oocytes injected with the hOAT4 E278K mutant was reduced compared with wild-type hOAT4. Km values for wild type and E278K were $0.7{\mu}M$ and $1.2{\mu}M$, and Vmax values were 1.8 and 0.47 pmol/oocyte/h, respectively. The present study demonstrates that hOAT4 variants can causing inter-individual variation in anionic drug uptake and, therefore, could be used as markers for certain diseases including osteoporosis.

• The Korean Journal of Physiology and Pharmacology
• /
• 제19권4호
• /
• pp.319-325
• /
• 2015

Among solute carrier proteins, the organic anion transporters (OATs) play an important role for the elimination or reabsorption of endogenous and exogenous negatively charged anionic compounds. Among OATs, SLC22A9 (hOAT7) transports estrone sulfate with high affinity. The net decrease of estrogen, especially in post-menopausal women induces rapid bone loss. The present study was performed to search the SNP within exon regions of SLC22A9 in Korean females with osteoporosis. Fifty healthy controls and 50 osteoporosis patients were screened for the genetic polymorphism in the coding region of SLC22A9 using GC-clamped PCR and denaturing gradient gel electrophoresis (DGGE). Six SNPs were found on the SLC22A9 gene from Korean women with/without osteoporosis. The SNPs were located as follows: two SNPs in the osteoporosis group (A645G and T1277C), three SNPs in the control group (G1449T, C1467T and C1487T) and one SNP in both the osteoporosis and control groups (G767A). The G767A, T1277C and C1487T SNPs result in an amino acid substitution, from synonymous vs nonsynonymous substitution arginine to glutamine (R256Q), phenylalanine to serine (F426S) and proline to leucine (P496L), respectively. The Km values and Vmax of the wild type, R256Q, P496L and F426S were 8.84, 8.87, 9.83 and $12.74{\mu}M$, and 1.97, 1.96, 2.06 and 1.55 pmol/oocyte/h, respectively. The present study demonstrates that the SLC22A9 variant F426S is causing inter-individual variation that is leading to the differences in transport of the steroid sulfate conjugate (estrone sulfate) and, therefore this could be used as a marker for certain disease including osteoporosis.

• Clinical and Experimental Reproductive Medicine
• /
• 제48권4호
• /
• pp.374-379
• /
• 2021

Objective: We aimed to evaluate associations between the ratio of serum estrone (E1) to estradiol (E2) and parameters related to serum glucose metabolism and insulin resistance in women with polycystic ovary syndrome (PCOS). Methods: In total, 133 women between the ages of 18 and 35 diagnosed with PCOS were enrolled in this study. All participants with PCOS underwent blood tests to determine hormonal and biochemical metabolic parameters and a standard 2-hour 75-g oral glucose tolerance test. They were divided into two groups according to the serum E1-to-E2 ratio: group 1 (E1/E2 ratio <2.0) and group 2 (E1/E2 ratio ≥2.0). Results: In the comparative analysis, the waist-to-hip ratio (WHR) was the only clinical variable that was significantly different between the two groups. Patients with a higher E1/E2 ratio showed higher fasting insulin levels, homeostasis model for insulin resistance, and postprandial glucose level at 2 hours (PPG2). In a correlation analysis, only PPG2 was significantly related to the serum E1/E2 ratio. However, after controlling for the confounding effects of body mass index (BMI) and WHR, fasting glucose was also significantly correlated with the serum E1/E2 ratio. Conclusion: Women with PCOS with a higher serum E1/E2 ratio were found to be more likely to show higher fasting insulin and postprandial glucose levels. Significant correlations were found between the serum E1/E2 ratio and both fasting and postprandial serum glucose levels after adjusting for BMI and WHR in women with PCOS.

• The Plant Pathology Journal
• /
• 제27권4호
• /
• pp.349-353
• /
• 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.

• Biomolecules & Therapeutics
• /
• 제20권6호
• /
• pp.556-561
• /
• 2012

Steroid sulfatase (STS) is responsible for the conversion of estrone sulfate to estrone that can stimulate growth in endocrine-dependent tumors such as prostate cancer. Although STS is considered as a therapeutic target for the estrogen-dependent diseases, cellular function of STS are still not clear. Previously, we found that tumor necrosis factor (TNF)-${\alpha}$ significantly enhances steroid sulfatase expression in PC-3 human prostate cancer cells through PI3K/Akt-dependent pathways. Here, we studied whether bacterial lipopolysaccharides (LPS) which are known to induce TNF-${\alpha}$ may increase STS expression. Treatment with LPS in PC-3 cells induced STS mRNA and protein in concentration- and time-dependent manners. Using luciferase reporter assay, we found that LPS enhanced STS promoter activity. Moreover, STS expression induced by LPS increased PC-3 tumor cell migration determined by wound healing assay. We investigated that LPS induced IL-6 expression and IL-6 increased STS expression. Taken together, these data strongly suggest that LPS induces STS expression through IL-6 pathway in human prostate cancer cells.

• Asian-Australasian Journal of Animal Sciences
• /
• 제16권9호
• /
• pp.1254-1260
• /
• 2003

The purpose of this study firstly was conducted to establish a radioimmunoassay (RIA) of estrone sulfate ($E_1S$), secondly to monitor the reproductive status of dairy cows using their urine samples. Urine and blood samples were collected in series within a day from four pregnant Holstein-friesian cows to evaluate the relationship between $E_1S$ levels in blood and urine with or without urinary creatinine basis. The urine was then collected biweekly from three cows in estrous and those artificially inseminated; collection from pregnant cows was made on a monthly basis. Results indicated that sensitivity for the $E_1S$ RIA was 5 pg/tube and the recovery rate was 100%. The daily urinary creatinine concentrations fluctuated within a day, but changes were slighter in midday, whereas the changes of concentrations of $E_1S$ in urine were relatively smaller. The concentrations of serum $E_1S$ during the estrous cycle were undetectable due to the limitation of assay, but the urinary $E_1S$ level could be measured with no obvious changes during the cycle. The urinary $E_1S$ levels increased remarkably around 7.7 to 8.3 ng/ml, 80 to 100 days after pregnancy but the serum $E_1S$ levels did not elevate until 120 to 150 days. The level of $E_1S$ increased gradually during pregnancy and eventually reached its peak before parturition at around 40 ng/ml and finally decreased to its basal level 2 days postparturition. During pregnancy, $E_1S$ concentrations of urine increased earlier than those in blood. The correlation coefficients between urinary and serum $E_1S$ concentration during pregnancy and postparturm were higher than those adjusted with creatinine (creatinine ratio). The concentrations of $E_1S$ in urine could be maintained unchanged for 8 days storing the samples in room temperature, which was extended to 8 days when the samples were pretreated by boiling for 30 minutes or treated with autoclave. In conclusion urinary $E_1S$ concentrations can be used directly for monitoring the pregnant status and fetal viability of dairy cows and can assist accurate confirmation of pregnancy in cows at least 80 to 100 days after insemination much earlier than by serum $E_1S$.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.177.2-178
• /
• 2003

Pomegranate, a small tree originating in Orient, belongs to Punicaceae family. The seeds contain an oil of which about 80％ is rare trans 18 carbon fatty acid (punicic acid), and have highest botanical concentration of a sex steroid, estrone. Pharmacological properties of pomegranate extract have been studied, with anti-microbial, anti-parasitic, anti-viral. and anti-cancer effects. (omitted)

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2003년도 춘계학술대회 논문집
• /
• pp.64-64
• /
• 2003

Pomegranate, a small tree originating in Orient, belongs to Punicaceae family. The seeds contain an oil of which about 80% is rare trans 18 carbon fatty acid (punicic acid), and have highest botanical concentration of a sex steroid, estrone. Pharmacological properties of pomegranate extract have been studied, with anti-microbial, anti-parasitic, anti-viral, and anti-cancer effects. (omitted)

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1992년도 제1회 신약개발 연구발표회 초록집
• /
• pp.21-21
• /
• 1992

녹용은 한방에서 신경조절 약화, 신체발육부진, 허약체질 등에 사용되는 강장제로서 인삼과 더불어 중요한 약재 중의 하나이지만 아직까지 유효 성분이 밝혀져 있지 않다. 알려진 녹용의 성분으로 collagen, acid mucopolysaccharide, 중성지질, 당지질, ganglioside, 인지질, proteolipid, prostaglandins, estrone, estradiol, cholesterol, its ester, 7-keto-cholesterol, 7$\alpha$-hydroxycholesterol , 7$\beta$-hydroxycholesterol , p-hydroxy-benzaldehyde, uracil, uridine, hypoxanthine, nicotinic acid, creatinine urea 등이 보고되었다. 이와 같은 성분들은 동물조직에서 공통적으로 발견되는 것들로서 녹용의 특이성분이라 부르기 어렵다. 그러나 uracil, uridine, hypoxanthine과 같은 핵산염기 관련 성분은 녹용에 비교적 함량이 많고, 이중에서 hypoxanthine은 monoamine oxidase-B에 대한 저해작용이 있으므로 주목할 필요성이 있다.

• 분석과학
• /
• 제21권6호
• /
• pp.526-534
• /
• 2008

가축의 생산성 향상을 위해 투여될 수 있는 천연호르몬과 합성 호르몬제 등의 내분비계장애물질에 대하여 기존의 분석 방법을 개선 및 확립하고, 이를 토대로 국내에 유통 중인 육류 및 내장부위 중소간에 대해 호르몬 성분의 분포정도를 확인하였다. Estrogens ($17{\beta}$-estradiol, $17{\alpha}$-estradiol, estrone), androgens ($17{\beta}$-testosterone, $17{\alpha}$-testosterone), gestagens (progesterone)의 천연호르몬 6종과 합성호르몬 3종 DES, RALs (zeranol, taleranol)을 모니터링 대상 호르몬으로 GC-MS로 분석하였으며, 이로부터 호르몬의 background level을 측정하고, 상대적으로 호르몬제 등이 잔류될 수 있는 간 등의 장기에 대한 분포조사를 실시하였다. 전체 150건의 시료 중 합성 호르몬제는 검출되지 않았으며, 천연호르몬제는 내인성으로 존재하는 progesterone이 일반적인 농도 범위를 보였다.