The scientific framework concerning estrogen effects on different tissues has expanded enormously during the last decades, when estrogen receptor （ER） subtypes were identified. Estrogens are not only essential for t...The scientific framework concerning estrogen effects on different tissues has expanded enormously during the last decades, when estrogen receptor （ER） subtypes were identified. Estrogens are not only essential for the female reproductive system, but they also control fundamental functions in other tissues including the cardiovascular system, bone, brain and liver. Recently, estrogens have been shown to target the biliary tree, where they modulate the proliferative and secretory activities of cholangiocytes, the epithelial cells lining bile ducts. By acting on both estrogen receptors （ER-α） and （ER-β） subtypes, and by activating either genomic or non-genomic pathways, estrogens play a key role in the complex loop of growth factors and cytokines, which modulates the proliferative response of cholangiocytes to damage. Specifically, estrogens activate intracellular signalling cascades JERK1/2 （extracellular regulated kinases 1/2, PI3-kinase/AKT （phosphatidylinositol-3＇ kinase/AKT）] typical of growth factors such as insulin like growth factor （IGF1）, nerve growth factor （NGF） and vascular endothelial growth factor （VEGF）, thus potentiating their action. In addition, estrogens stimulate the secretion of different growth factors in proliferating cholangiocytes. This review specifically deals with the recent advances related to the role and mechanisms by which estrogens modulate cholangiocyte functions in normal and pathological conditions.展开更多
Aim： To investigate the effects of 17β-estradiol （E2）, Peganum harmala extract （PHE） and caloric restriction （CR） on various testis parameters during aging. Methods： Twelve-month-old male rats were treated fo...Aim： To investigate the effects of 17β-estradiol （E2）, Peganum harmala extract （PHE） and caloric restriction （CR） on various testis parameters during aging. Methods： Twelve-month-old male rats were treated for 6 months with either E2 or PHE, or submitted to CR （40%）. Results： Our results show that estrogens and CR are able to protect the male gonad by preventing the decrease of testosterone and E2 levels as well as the decrease of aromatase and estrogen receptor gene expressions. Indeed, E2, PHE and CR treatments induced an increase in the superoxide dismutase activities and decreased the activity of testicular enzymes： gamma-glutamyl transferase, alkaline phosphatase, lactate deshydrogenase as well as the aspartate and lactate transaminases in aged animals. In addition, the testicular catalase and gluthatione peroxidase activities were enhanced in E2, PHE and CR-treated rats compared to untreated animals at 18 months of age. Moreover, the positive effects of estradiol, PHE and CR were further supported by a lower level of lipid peroxidation. Recovery of spermatogenesis was recorded in treated rats. Conclusion： Besides a low caloric diet which is beneficial for spermatogenesis, a protective antioxydant role of estrogens is suggested. Estrogens delay testicular cell damage, which leads to functional senescence and, therefore, estrogens are helpful in protecting the reproductive functions from the adverse effects exerted by reactive oxygen species （ROS） produced in large quanti- ties in the aged testis.展开更多
The main estrogens:estradiol,estrone,and their acyl-esters have been studied essentially related to their classical estrogenic and pharmacologic functions.However,their main effect in the body is probably the sustaine...The main estrogens:estradiol,estrone,and their acyl-esters have been studied essentially related to their classical estrogenic and pharmacologic functions.However,their main effect in the body is probably the sustained control of core energy metabolism.Estrogen nuclear and membrane receptors show an extraordinary flexibility in the modulation of metabolic responses,and largely explain gender and age differences in energy metabolism:part of these mechanisms is already sufficiently known to justify both.With regard to energy,the estrogen molecular species act essentially through four key functions:(1)Facilitation of insulin secretion and control of glucose availability;(2)Modulation of energy partition,favoring the use of lipid as the main energy substrate when more available than carbohydrates;(3)Functional protection through antioxidant mechanisms;and(4)Central effects(largely through neural modulation)on whole body energy management.Analyzing the different actions of estrone,estradiol and their acyl esters,a tentative classification based on structure/effects has been postulated.Either separately or as a group,estrogens provide a comprehensive explanation that not all their quite diverse actions are related solely to specific molecules.As a group,they constitute a powerful synergic action complex.In consequence,estrogens may be considered wardens of energy homeostasis.展开更多
AIM:To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHOD...AIM:To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS:A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS:No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69vs 37.708 ± 5.31,P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13,P = 0.04), mRNA (2.278 ± 1.19vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67,P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06vs 0.532 ± 0.11,P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION:The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.展开更多
Several epidemiological,cellular,and molecular studies demonstrate the role of environmental chemicals with endocrine disrupting activities,typical of Westernized societies,in the pathogenesis of numerous diseases inc...Several epidemiological,cellular,and molecular studies demonstrate the role of environmental chemicals with endocrine disrupting activities,typical of Westernized societies,in the pathogenesis of numerous diseases including cancer.Nonetheless this information,the design and execution of studies on endocrine disruptors are not yet cognizant that the specific actions of individual hormones often change with development and ageing,they may be different in males and females and may be mediated by different receptors isoforms expressed in different tissues or at different life stages.These statements are particularly true when assessing the hazard of endocrine disruptors against 17β-estradiol(E2)actions in that this hormone is crucial determinant of sexrelated differences in anatomical,physiological,and behavioral traits which characterize male and female physiology.Moreover,E2 is also involved in carcinogenesis.The oncogenic effects of E2 have been investigated extensively in breast and ovarian cancers where hormone-receptor modulators are now an integral part of targeted treatment.Little is known about the E2preventive signalling in colorectal cancer,although this disease is more common in men than women,the difference being more striking amongst pre-menopausal women and age-matched men.This review aims to dissect the role and action mechanisms of E2 in colorectal cancer evaluating the ability of estrogen disruptors(i.e.,xenoestrogens)in impair these E2 actions.Data discussed here lead to define the possible role of xenoestrogens in the impairment and/or activation of E2signals important for colorectal cancer prevention.展开更多
We established an improved method for the determination of four estrogens including estriol （E3）, 17β-estradiol （E2）, 17α-ethynyl- estrodiol （EE2） and estrone （E1） in water. The method consisted of solid-pha...We established an improved method for the determination of four estrogens including estriol （E3）, 17β-estradiol （E2）, 17α-ethynyl- estrodiol （EE2） and estrone （E1） in water. The method consisted of solid-phase extraction （0.5 L water） and subsequent analysis of analytes by ultra-performance liquid chromatography （UPLC） with an ultraviolet detector （UVD）. Base-line separation was achieved for all studied estrogens using a column （50 mm × 2.1 mm） packed with 1.7 μm particle size stationary phase. Recovery was higher than 88% and detection limits ranged between 12.5–23.7 ng/L for the four estrogens, with the RSD ranging from 7% to 11%. The method was successfully applied to determine E2 and EE2 in simulated natural water, which found that about 70% of E2 was degraded （with a half-life of about 30 hr） within 48 hr and about 55% of EE2 was degraded （with a half-life of about 36 hr）. Low levels of E1 were found, however E3 was undetectable during the process.展开更多
Objective To investigate the protective effect of 17β-estradiol （E2）, peganum harmala extract （PHE） administration and calorie restriction （CR） treatment （60%） on oxidative stress and hepato-toxicity in aged ...Objective To investigate the protective effect of 17β-estradiol （E2）, peganum harmala extract （PHE） administration and calorie restriction （CR） treatment （60%） on oxidative stress and hepato-toxicity in aged rats. Methods Eighteen months old animals that were treated at the age of 12 months were divided into 4 groups： normal control group with free access to food, E2 treatment group, PHE treatment group and CR treatment group of the food given to control group. Six male rats at the age of 4 months were used as a reference group. Results Aging significantly decreased superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GPX）, and increased lactate deshydrogenase （LDH）, gamma-glyiamyl transferase （GGT）, pbosphatase alkalines （PAL）, aspartate and lactate transaminase （AST and ALT） activities in the liver. Aging also induced an increased lipid peroxidation level, histological changes and a decreased E2 level. However, treatment with E2, PHE, and CR increased 17β-estradiol, and decreased hepatic dysfunction parameters and lipid peroxidation as well as histological changes in the liver of aged rats. Conclusion The antioxidant and hepatoprotective activity of PHE and CR is possibly attributed to its ability to increase E2 level, which as an antioxidant, acts as a scavenger of ROS. Further studies on the pharmaceutical functions of E2 in males may contribute to its clinical application.展开更多
A rapid, cost effective and reliable analytical method was developed and validated for the simultaneous determination of four estrogens (17 β-estradiol, 17 α-ethinylestradiol, estrone, and estriol) in compost sample...A rapid, cost effective and reliable analytical method was developed and validated for the simultaneous determination of four estrogens (17 β-estradiol, 17 α-ethinylestradiol, estrone, and estriol) in compost samples from the biodegradation of biological infectious hazardous wastes. Ultrasonic solvent extraction, using methanol as extraction solvent, coupled with SPE clean-up, using cartridges HLB 60 mg - 6 ml Supelco®<sup></sup> and acetonitrile for reconstitution of eluents, was used for the simultaneous extraction of the four estrogens. Mean recoveries in the range of 98% - 107% were obtained. All compounds were separated in a single gradient run by UHPLC Kinetex<sup>TM</sup> 2.6 μm XB-C18 100 ÅLC (50 × 4.6 mm) column. Analytes were detected via multiple reaction monitoring (MRM) using an AB SCIEX API-5000TM triple quadrupole (Applied Biosystems/MDS SCIEX) with electrospray ionization in negative mode. Isocratic mobile phase of Water:ACN (50:50) resulted to be the optimum. Limits of detection and quantification were on the order of 0.66 ng·g<sup>-1</sup> and 2 ng·g<sup>-1</sup> for all the estrogens. These limits were lower than most of the values reported in the literature for similar matrices. Suitable level of linearity, good repeatability and reproducibility with coefficients of variation is lower than 11.7%, 6.8% and 8.3%, respectively.展开更多
In order to obtain information on the biodegradation potential of biofilms involved in the removal of natural estrogens by biological activated carbon (BAC) columns, batch degradation of estrone (E1) and 17β-estradio...In order to obtain information on the biodegradation potential of biofilms involved in the removal of natural estrogens by biological activated carbon (BAC) columns, batch degradation of estrone (E1) and 17β-estradiol (E2) at temperature of 5℃, 20℃ and 35℃ by biofilms from four BAC columns (packed with activated carbon of particle size ranging from 0.5 - 0.59 mm and 1.0 - 1.19 mm into two bed depths) was studied. The results indicated that E2 was degraded faster by than E1 at all three temperatures and with the increasing of temperature, the amount of E1 converted from E2 increased. By fitting observed concentration data with a first-order rate expression, the bio-mass based degradation rate constants (kVSS) for E1 and E2 under all experimental conditions were estimated and linear relationship between lnkVSS and 1/T (T = absolute temperature) was demonstrated, resulting that with the increasing of the experimental temperature, degradation rate of biofilms for both E1 and E2 increased, and the increasing rate for E2 was higher than that for E1.展开更多
This review focuses on the role of estrogen in men, mainly in male reproduction. The continuing increase in data obtained, and recent discoveries in this area will enable a better understanding of male physiology; the...This review focuses on the role of estrogen in men, mainly in male reproduction. The continuing increase in data obtained, and recent discoveries in this area will enable a better understanding of male physiology; these, in turn, will have important clinical implications.展开更多
Sex hormone estrogen is one of the most active intrinsic angiogenesis regulators; its therapeutic use has been limited due to its carcinogenic potential. Plant-derived phytoestrogens are attractive alternatives, but r...Sex hormone estrogen is one of the most active intrinsic angiogenesis regulators; its therapeutic use has been limited due to its carcinogenic potential. Plant-derived phytoestrogens are attractive alternatives, but reports on their angiogenic activities often lack in-depth analysis and sometimes are controversial. Herein, we report a data-mining study with the existing literature, using IPA system to classify and characterize phytoestrogens based on their angiogenic properties and pharmacological consequences. We found that pro-angiogenic phytoestrogens functioned predominantly as cardiovascular protectors whereas anti-angiogenic phytoestrogens played a role in cancer prevention and therapy. This bidirectional regulation were shown to be target-selective and, for the most part, estrogen-receptor-dependent. The transactivation properties of ERa and ERβ by phytoestrogens were examined in the context of angiogenesis-related gene transcription. ERa and ERβ were shown to signal in opposite ways when complexed with the phytoestrogen for bidirectional regulation of angiogenesis. With ERa, phytoestrogen activated or inhibited transcription of some angiogenesis-related genes, resulting in the promotion of angiogenesis, whereas, with ERβ, phytoestrogen regulated transcription of angiogenesis-related genes, resulting in inhibition of angiogenesis. Therefore, the selectivity of phytoestrogen to ERa and ERβ may be critical in the balance of pro- or anti-angiogenesis process.展开更多
Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conver...Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone （T） to estradiol （E2） by aromatase, or to dihydrotestosterone by 5（x-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of （high resolution） peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refined our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen deficiency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the field of sex steroid actions in male bone homeostasis.展开更多
The discharge of steroid estroens from sewage treatment works (STW) is to be regulated by Environmental Quality Standard in the UK,thus requiring the understanding of removal characteristics of steroid estroens in tri...The discharge of steroid estroens from sewage treatment works (STW) is to be regulated by Environmental Quality Standard in the UK,thus requiring the understanding of removal characteristics of steroid estroens in trickling filters to benefit UK water industry with trickling filters used in 75% STWs. Two pilot-scale trickling filters were operated in parallel to treat synthetic sewage spiked with oestrone (E1),oestradiol (E2) and 17α-ethinyl oestradiol (EE2) at environmentally related concentrations. Control experiments show that biodegradation is the dominant removal mechanism although adsorption onto biofilm solids prior to biodegradation would be part of the overall mechanisms of estrogen removal. Approximately 44.7%-58.9% is removed by the pilot trickling filter normally operated,whilst the 1:1 recirculation increases 29.0%-32.2% estrogen removals by improved wetting rate and hydraulic retention time supported by tracer experiment with lithium chloride. Extra feed solids with 32.0% higher suspended solids levels inhibited estrogen removals by 10.8%-34.4% rather than helping bridge adsorption to the biofilm,and the change of particle characteristics with higher adsorption potency would benefit the removal.展开更多
The feasibility of using two types of biochars to reduce steroid hormone pollution from poultry and swine manure application on agricultural land was evaluated. The sorption affinity and desorption resistance of softw...The feasibility of using two types of biochars to reduce steroid hormone pollution from poultry and swine manure application on agricultural land was evaluated. The sorption affinity and desorption resistance of softwood and hardwood biochars were also determined for two estrogen hormones, 17β-estradiol （E2） and its primary metabolite estrone （E1）. The softwood and hardwood biochars demonstrated high retention capacity for both estrogens. The effective distribution coefficient （Kedff） of soil-softwood-derived biochar （SBS450） was significantly higher than soil-hardwood-derived biochar （SBH750）, indicating the stronger sorption affinity of SBS450 for estrogens. To validate the laboratory results, a field lysimeter experiment was conducted to study the fate and transport of E2 and E1 in soil and leachate in the presence of 1% softwood-biochar （BS450） in topsoil and to compare it with soil without any amendments. The spatio-temporal distribution of both estrogens was monitored at four depths over a 46-day period. The lysimeters, in which the surface layer of soil was amended with biochar, retained significantly higher concentrations of both estrogen hormones. Although they leached through the soil and were detected in leachates, collected at 1.0 m depth, the concentrations were significantly lower in the leachate collected from biochar-amended lysimeters. The result confirmed the efficacy of biochar amendment as a remediation technique to alleviate the manure-borne hormonal pollution of groundwater.展开更多
Menopausal hormone therapy(MHT)has been widely used for the clinical treatment of symptoms associated with menopause in women.However,the exact nature of the relationship between MHT and the increased risk of breast c...Menopausal hormone therapy(MHT)has been widely used for the clinical treatment of symptoms associated with menopause in women.However,the exact nature of the relationship between MHT and the increased risk of breast cancer has not been fully elucidated.The results of the Women’s Health Initiative’s randomized controlled clinical studies showed that estrogen monotherapy was associated with a lower incidence of breast cancer as compared to estrogen-progesterone combined therapy,with an elevated risk of breast cancer.The evidence currently available from randomized trials and observational studies is based on data from different populations,drug formulations,and routes of administration.Even though the risks of MHT and breast cancer have received a great deal of attention,information regarding the unpredictable toxicological risks of estrogen and progestogen metabolism needs to be further analyzed.Furthermore,the diversity and complexity of the metabolic pathways of estrogen and different progestogens as well as the association of the different estrogen and progestogen metabolites with the increased risk of breast cancer need to be adequately studied.Therefore,this review aimed to describe the biological effects of estrogen,progesterone,and their metabolites on the proliferation of breast cancer cells,based on relevant basic research and clinical trials,to improve our understanding of the biological functions of estrogen and progestogen as well as the safety of MHT.展开更多
Estrogen hormones as a group of endocrine disruptive compounds （EDC） can interfere with endocrine system in humans and animals. The goal of this study was to investigate the elimination rate of Estrone （El）, 17β-...Estrogen hormones as a group of endocrine disruptive compounds （EDC） can interfere with endocrine system in humans and animals. The goal of this study was to investigate the elimination rate of Estrone （El）, 17β-estradiol （E2） and 17α-ethinyl estradiol （EE2） in Moving Bed Bioreactor （MBBR）. These analytes extracted by Dispersive Liquid-Liquid Microextraction （DLLME） technique, followed by derivatization, and detected by GC/MS. Estrogen removal efficiency in MBBR improved at high solid retention times （SRTs）, which notion is owing to development ofnitrification. Estrogenspecificremovalratewasbetween 0,22-1.45μg.（gVSS） 1.d -1 for natural and synthetic hormones. The adsorption rate was 0.9%-3.2% 0-1.3%, and 0.7%-5.7% for E1, E2, and EE2, respectively. In addition, the biodegradation rates were more than 95% for these compounds. These results illustrated that in MBBR, the hiodegradation and the adsorption to biomass are considered as two significant routes for elimination of estrogenic compounds. As a whole, the deterioration rate of estrogens enhanced by MBBR compared to other biological wastewater treatment processes such as conventional activated sludge.展开更多
Treatments of estrogens such as Estrone （El）, Estradiol （E2） and Ethinylestradiol （EE2） were conducted using an electrolytic reactor equipped with multi-packed granular glassy carbon electrodes. Experimental res...Treatments of estrogens such as Estrone （El）, Estradiol （E2） and Ethinylestradiol （EE2） were conducted using an electrolytic reactor equipped with multi-packed granular glassy carbon electrodes. Experimental results showed that El, E2 and EE2 were oxidized in the range of 0.45-0.85 V and were removed through electro-polymerization. Observed data from continuous experiments were in good agreement with calculated results by a mathematical model constructed based on mass transfer limitation. In continuous treatment of trace estrogens （1 μg/L）, 98% of El, E2 and EE2 were stably removed. At high loading rate （100 μg/L）, removal efficiency of E1 was kept around 74%-88% for 21 days, but removal efficiency reduced due to passivation of electrodes. However, removal efficiency was recovered after electrochemical regeneration of electrodes in presence of ozone. Electric energy consumption was observed in the range of 1-2 Wh/m3. From these results, we concluded that the present electrochemical process would be an alternative removal of estrogens.展开更多
On study of the effects of estrogen deficiency on anxiety disorder by using ovariectomised animals, one discrepancy was the difference in behavioral testing delay following ovariectomy and the paradigms used. Thus, th...On study of the effects of estrogen deficiency on anxiety disorder by using ovariectomised animals, one discrepancy was the difference in behavioral testing delay following ovariectomy and the paradigms used. Thus, the aim of this study was to evaluate the anxiogenic effects of fourteen-day estrogen decline subsequent to ovariectomy on Wistar rats using EPM （elevated plus-maze） and open field tests. As results, fourteen days of estrogens decline has induced an increase of anxiety-related behaviour by a reduction of the percentage of the number of entries into the open arm （p 〈 0.01） and an increase of the percentage of the number of entries into the closed arm （/9 〈 0.01） during the elevated plus-maze test. This anxiety-like behaviour was confirmed on the open field test by a reduction of time spent in the centre of the arena （p 〈 0.05） as well as a reduction of crossing （p 〈 0.05） and an increase of the weight of faecal boli （p 〈 0.05） and grooming （p 〈 0.01）. Meanwhile, the administration of diazepam or estradiol valerate （1 mg/kg BW each） has corrected the anxious-like behaviour in both tests paradigms. These results suggest that fourteen days of estrogens decline was associated with an anxiety-related behaviour. This experimental model can constitute an excellent tool for the study of anxiolytic substances in menopause-related anxiety.展开更多
Oral estrogens are directly associated with changes in plasma levels of coagulation proteins. Thus, the detection of any variation in protein concentrations due to estrogen contraceptives, by a simultaneous analysis o...Oral estrogens are directly associated with changes in plasma levels of coagulation proteins. Thus, the detection of any variation in protein concentrations due to estrogen contraceptives, by a simultaneous analysis of both coagulation proteins and estrogens, would be a very informative tool. In the present study, the merit of photo-selected reaction monitoring （SRM）, a new analytical tool, was evaluated towards estrogens detection in plasma. Then, SRM and photo-SRM detection modes were combined for the simultaneous analysis of estrogen molecules together with heparin co-factor and factor XIIa, two proteins involved in the coagulation cascade. This study shows that photo-SRM could open new multiplexed analytical routes.展开更多
Highly sensitive voltammetric method for the determination of estrogens, based on the enhancement effect of cetyltrimethylammonium bromide (CTAB) has been described. In the presence of CTAB, the oxidation peak current...Highly sensitive voltammetric method for the determination of estrogens, based on the enhancement effect of cetyltrimethylammonium bromide (CTAB) has been described. In the presence of CTAB, the oxidation peak currents of estrogens (estradiol, estrone, estriol, estradiol valerate and diethylstilbestrol) as the carbon paste electrode (CPE) increased significantly after open-circuit accumulation. The peak current was proportional to the concentration of estradiol over the range from 5×10?9 to 2.5×10?6 mol·L?1. The detection limit was 8×10?10 mol·L?1 at 6 min of accumulation. The total amounts of estrogens in the blood serums were determined and the average recovery was 104.92%. Under the conditions used, the electrode process of estradiol was examined the mechanism for peak current enhancement was also discussed.展开更多
基金MIUR grants PRIN, No.2003060498_002 and No. 2005067975_002 to Dr. Alvaro and by a grant award from Scott & White Hospital and The Texas A&M University System Health Science Center, a VA Merit Award, a VA Research Scholar Award and the NIH grants DK58411 and DK062975 to Dr. Alpini
文摘The scientific framework concerning estrogen effects on different tissues has expanded enormously during the last decades, when estrogen receptor （ER） subtypes were identified. Estrogens are not only essential for the female reproductive system, but they also control fundamental functions in other tissues including the cardiovascular system, bone, brain and liver. Recently, estrogens have been shown to target the biliary tree, where they modulate the proliferative and secretory activities of cholangiocytes, the epithelial cells lining bile ducts. By acting on both estrogen receptors （ER-α） and （ER-β） subtypes, and by activating either genomic or non-genomic pathways, estrogens play a key role in the complex loop of growth factors and cytokines, which modulates the proliferative response of cholangiocytes to damage. Specifically, estrogens activate intracellular signalling cascades JERK1/2 （extracellular regulated kinases 1/2, PI3-kinase/AKT （phosphatidylinositol-3＇ kinase/AKT）] typical of growth factors such as insulin like growth factor （IGF1）, nerve growth factor （NGF） and vascular endothelial growth factor （VEGF）, thus potentiating their action. In addition, estrogens stimulate the secretion of different growth factors in proliferating cholangiocytes. This review specifically deals with the recent advances related to the role and mechanisms by which estrogens modulate cholangiocyte functions in normal and pathological conditions.
文摘Aim： To investigate the effects of 17β-estradiol （E2）, Peganum harmala extract （PHE） and caloric restriction （CR） on various testis parameters during aging. Methods： Twelve-month-old male rats were treated for 6 months with either E2 or PHE, or submitted to CR （40%）. Results： Our results show that estrogens and CR are able to protect the male gonad by preventing the decrease of testosterone and E2 levels as well as the decrease of aromatase and estrogen receptor gene expressions. Indeed, E2, PHE and CR treatments induced an increase in the superoxide dismutase activities and decreased the activity of testicular enzymes： gamma-glutamyl transferase, alkaline phosphatase, lactate deshydrogenase as well as the aspartate and lactate transaminases in aged animals. In addition, the testicular catalase and gluthatione peroxidase activities were enhanced in E2, PHE and CR-treated rats compared to untreated animals at 18 months of age. Moreover, the positive effects of estradiol, PHE and CR were further supported by a lower level of lipid peroxidation. Recovery of spermatogenesis was recorded in treated rats. Conclusion： Besides a low caloric diet which is beneficial for spermatogenesis, a protective antioxydant role of estrogens is suggested. Estrogens delay testicular cell damage, which leads to functional senescence and, therefore, estrogens are helpful in protecting the reproductive functions from the adverse effects exerted by reactive oxygen species （ROS） produced in large quanti- ties in the aged testis.
文摘The main estrogens:estradiol,estrone,and their acyl-esters have been studied essentially related to their classical estrogenic and pharmacologic functions.However,their main effect in the body is probably the sustained control of core energy metabolism.Estrogen nuclear and membrane receptors show an extraordinary flexibility in the modulation of metabolic responses,and largely explain gender and age differences in energy metabolism:part of these mechanisms is already sufficiently known to justify both.With regard to energy,the estrogen molecular species act essentially through four key functions:(1)Facilitation of insulin secretion and control of glucose availability;(2)Modulation of energy partition,favoring the use of lipid as the main energy substrate when more available than carbohydrates;(3)Functional protection through antioxidant mechanisms;and(4)Central effects(largely through neural modulation)on whole body energy management.Analyzing the different actions of estrone,estradiol and their acyl esters,a tentative classification based on structure/effects has been postulated.Either separately or as a group,estrogens provide a comprehensive explanation that not all their quite diverse actions are related solely to specific molecules.As a group,they constitute a powerful synergic action complex.In consequence,estrogens may be considered wardens of energy homeostasis.
基金Supported by Wholly granted from R and D, CMD Pharma Limited, United Kingdom
文摘AIM:To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS:A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS:No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69vs 37.708 ± 5.31,P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13,P = 0.04), mRNA (2.278 ± 1.19vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67,P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06vs 0.532 ± 0.11,P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION:The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.
文摘Several epidemiological,cellular,and molecular studies demonstrate the role of environmental chemicals with endocrine disrupting activities,typical of Westernized societies,in the pathogenesis of numerous diseases including cancer.Nonetheless this information,the design and execution of studies on endocrine disruptors are not yet cognizant that the specific actions of individual hormones often change with development and ageing,they may be different in males and females and may be mediated by different receptors isoforms expressed in different tissues or at different life stages.These statements are particularly true when assessing the hazard of endocrine disruptors against 17β-estradiol(E2)actions in that this hormone is crucial determinant of sexrelated differences in anatomical,physiological,and behavioral traits which characterize male and female physiology.Moreover,E2 is also involved in carcinogenesis.The oncogenic effects of E2 have been investigated extensively in breast and ovarian cancers where hormone-receptor modulators are now an integral part of targeted treatment.Little is known about the E2preventive signalling in colorectal cancer,although this disease is more common in men than women,the difference being more striking amongst pre-menopausal women and age-matched men.This review aims to dissect the role and action mechanisms of E2 in colorectal cancer evaluating the ability of estrogen disruptors(i.e.,xenoestrogens)in impair these E2 actions.Data discussed here lead to define the possible role of xenoestrogens in the impairment and/or activation of E2signals important for colorectal cancer prevention.
基金supported by the Shandong Natural Science Foundation(No.ZR2010BQ025)the National High Technology Research and Development Program(863)of China(No.200905019-3)the Open Fund of State Oceanic Administration(No.MBSMAT-2009.06)
文摘We established an improved method for the determination of four estrogens including estriol （E3）, 17β-estradiol （E2）, 17α-ethynyl- estrodiol （EE2） and estrone （E1） in water. The method consisted of solid-phase extraction （0.5 L water） and subsequent analysis of analytes by ultra-performance liquid chromatography （UPLC） with an ultraviolet detector （UVD）. Base-line separation was achieved for all studied estrogens using a column （50 mm × 2.1 mm） packed with 1.7 μm particle size stationary phase. Recovery was higher than 88% and detection limits ranged between 12.5–23.7 ng/L for the four estrogens, with the RSD ranging from 7% to 11%. The method was successfully applied to determine E2 and EE2 in simulated natural water, which found that about 70% of E2 was degraded （with a half-life of about 30 hr） within 48 hr and about 55% of EE2 was degraded （with a half-life of about 36 hr）. Low levels of E1 were found, however E3 was undetectable during the process.
基金supported by the Tunisian Ministry of Education and Scientific Research and the Faculty of Science,Sfax, Tunisia
文摘Objective To investigate the protective effect of 17β-estradiol （E2）, peganum harmala extract （PHE） administration and calorie restriction （CR） treatment （60%） on oxidative stress and hepato-toxicity in aged rats. Methods Eighteen months old animals that were treated at the age of 12 months were divided into 4 groups： normal control group with free access to food, E2 treatment group, PHE treatment group and CR treatment group of the food given to control group. Six male rats at the age of 4 months were used as a reference group. Results Aging significantly decreased superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GPX）, and increased lactate deshydrogenase （LDH）, gamma-glyiamyl transferase （GGT）, pbosphatase alkalines （PAL）, aspartate and lactate transaminase （AST and ALT） activities in the liver. Aging also induced an increased lipid peroxidation level, histological changes and a decreased E2 level. However, treatment with E2, PHE, and CR increased 17β-estradiol, and decreased hepatic dysfunction parameters and lipid peroxidation as well as histological changes in the liver of aged rats. Conclusion The antioxidant and hepatoprotective activity of PHE and CR is possibly attributed to its ability to increase E2 level, which as an antioxidant, acts as a scavenger of ROS. Further studies on the pharmaceutical functions of E2 in males may contribute to its clinical application.
文摘A rapid, cost effective and reliable analytical method was developed and validated for the simultaneous determination of four estrogens (17 β-estradiol, 17 α-ethinylestradiol, estrone, and estriol) in compost samples from the biodegradation of biological infectious hazardous wastes. Ultrasonic solvent extraction, using methanol as extraction solvent, coupled with SPE clean-up, using cartridges HLB 60 mg - 6 ml Supelco®<sup></sup> and acetonitrile for reconstitution of eluents, was used for the simultaneous extraction of the four estrogens. Mean recoveries in the range of 98% - 107% were obtained. All compounds were separated in a single gradient run by UHPLC Kinetex<sup>TM</sup> 2.6 μm XB-C18 100 ÅLC (50 × 4.6 mm) column. Analytes were detected via multiple reaction monitoring (MRM) using an AB SCIEX API-5000TM triple quadrupole (Applied Biosystems/MDS SCIEX) with electrospray ionization in negative mode. Isocratic mobile phase of Water:ACN (50:50) resulted to be the optimum. Limits of detection and quantification were on the order of 0.66 ng·g<sup>-1</sup> and 2 ng·g<sup>-1</sup> for all the estrogens. These limits were lower than most of the values reported in the literature for similar matrices. Suitable level of linearity, good repeatability and reproducibility with coefficients of variation is lower than 11.7%, 6.8% and 8.3%, respectively.
文摘In order to obtain information on the biodegradation potential of biofilms involved in the removal of natural estrogens by biological activated carbon (BAC) columns, batch degradation of estrone (E1) and 17β-estradiol (E2) at temperature of 5℃, 20℃ and 35℃ by biofilms from four BAC columns (packed with activated carbon of particle size ranging from 0.5 - 0.59 mm and 1.0 - 1.19 mm into two bed depths) was studied. The results indicated that E2 was degraded faster by than E1 at all three temperatures and with the increasing of temperature, the amount of E1 converted from E2 increased. By fitting observed concentration data with a first-order rate expression, the bio-mass based degradation rate constants (kVSS) for E1 and E2 under all experimental conditions were estimated and linear relationship between lnkVSS and 1/T (T = absolute temperature) was demonstrated, resulting that with the increasing of the experimental temperature, degradation rate of biofilms for both E1 and E2 increased, and the increasing rate for E2 was higher than that for E1.
文摘This review focuses on the role of estrogen in men, mainly in male reproduction. The continuing increase in data obtained, and recent discoveries in this area will enable a better understanding of male physiology; these, in turn, will have important clinical implications.
基金supported by National Natural Science Foundation of China(No.81274128)China National Funds for Distinguished Young Scientists(No.81125024)the Program of the State Key Development Program for Basic Research of China(No.2012CB723504)
文摘Sex hormone estrogen is one of the most active intrinsic angiogenesis regulators; its therapeutic use has been limited due to its carcinogenic potential. Plant-derived phytoestrogens are attractive alternatives, but reports on their angiogenic activities often lack in-depth analysis and sometimes are controversial. Herein, we report a data-mining study with the existing literature, using IPA system to classify and characterize phytoestrogens based on their angiogenic properties and pharmacological consequences. We found that pro-angiogenic phytoestrogens functioned predominantly as cardiovascular protectors whereas anti-angiogenic phytoestrogens played a role in cancer prevention and therapy. This bidirectional regulation were shown to be target-selective and, for the most part, estrogen-receptor-dependent. The transactivation properties of ERa and ERβ by phytoestrogens were examined in the context of angiogenesis-related gene transcription. ERa and ERβ were shown to signal in opposite ways when complexed with the phytoestrogen for bidirectional regulation of angiogenesis. With ERa, phytoestrogen activated or inhibited transcription of some angiogenesis-related genes, resulting in the promotion of angiogenesis, whereas, with ERβ, phytoestrogen regulated transcription of angiogenesis-related genes, resulting in inhibition of angiogenesis. Therefore, the selectivity of phytoestrogen to ERa and ERβ may be critical in the balance of pro- or anti-angiogenesis process.
文摘Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone （T） to estradiol （E2） by aromatase, or to dihydrotestosterone by 5（x-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of （high resolution） peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refined our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen deficiency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the field of sex steroid actions in male bone homeostasis.
基金Project (NDP2005UU) supported by UK EA National Demonstration Program on EDC removalProject (50808183) supported by the National Natural Science Foundation of ChinaProjects (CSTC2008BB7047,CSTC2009BB030) supported by the Natural Science Foundation of Chongqing,China
文摘The discharge of steroid estroens from sewage treatment works (STW) is to be regulated by Environmental Quality Standard in the UK,thus requiring the understanding of removal characteristics of steroid estroens in trickling filters to benefit UK water industry with trickling filters used in 75% STWs. Two pilot-scale trickling filters were operated in parallel to treat synthetic sewage spiked with oestrone (E1),oestradiol (E2) and 17α-ethinyl oestradiol (EE2) at environmentally related concentrations. Control experiments show that biodegradation is the dominant removal mechanism although adsorption onto biofilm solids prior to biodegradation would be part of the overall mechanisms of estrogen removal. Approximately 44.7%-58.9% is removed by the pilot trickling filter normally operated,whilst the 1:1 recirculation increases 29.0%-32.2% estrogen removals by improved wetting rate and hydraulic retention time supported by tracer experiment with lithium chloride. Extra feed solids with 32.0% higher suspended solids levels inhibited estrogen removals by 10.8%-34.4% rather than helping bridge adsorption to the biofilm,and the change of particle characteristics with higher adsorption potency would benefit the removal.
文摘The feasibility of using two types of biochars to reduce steroid hormone pollution from poultry and swine manure application on agricultural land was evaluated. The sorption affinity and desorption resistance of softwood and hardwood biochars were also determined for two estrogen hormones, 17β-estradiol （E2） and its primary metabolite estrone （E1）. The softwood and hardwood biochars demonstrated high retention capacity for both estrogens. The effective distribution coefficient （Kedff） of soil-softwood-derived biochar （SBS450） was significantly higher than soil-hardwood-derived biochar （SBH750）, indicating the stronger sorption affinity of SBS450 for estrogens. To validate the laboratory results, a field lysimeter experiment was conducted to study the fate and transport of E2 and E1 in soil and leachate in the presence of 1% softwood-biochar （BS450） in topsoil and to compare it with soil without any amendments. The spatio-temporal distribution of both estrogens was monitored at four depths over a 46-day period. The lysimeters, in which the surface layer of soil was amended with biochar, retained significantly higher concentrations of both estrogen hormones. Although they leached through the soil and were detected in leachates, collected at 1.0 m depth, the concentrations were significantly lower in the leachate collected from biochar-amended lysimeters. The result confirmed the efficacy of biochar amendment as a remediation technique to alleviate the manure-borne hormonal pollution of groundwater.
基金This study was supported by grants from the National Natural Science Foundation of China(Grant Nos.61673024 and 81971348)the Clinical Medicine Plus X-Young Scholar Project,Peking University,and the Fundamental Research Funds for the Central University(Grant No.PKU2018LCXQ001).
文摘Menopausal hormone therapy(MHT)has been widely used for the clinical treatment of symptoms associated with menopause in women.However,the exact nature of the relationship between MHT and the increased risk of breast cancer has not been fully elucidated.The results of the Women’s Health Initiative’s randomized controlled clinical studies showed that estrogen monotherapy was associated with a lower incidence of breast cancer as compared to estrogen-progesterone combined therapy,with an elevated risk of breast cancer.The evidence currently available from randomized trials and observational studies is based on data from different populations,drug formulations,and routes of administration.Even though the risks of MHT and breast cancer have received a great deal of attention,information regarding the unpredictable toxicological risks of estrogen and progestogen metabolism needs to be further analyzed.Furthermore,the diversity and complexity of the metabolic pathways of estrogen and different progestogens as well as the association of the different estrogen and progestogen metabolites with the increased risk of breast cancer need to be adequately studied.Therefore,this review aimed to describe the biological effects of estrogen,progesterone,and their metabolites on the proliferation of breast cancer cells,based on relevant basic research and clinical trials,to improve our understanding of the biological functions of estrogen and progestogen as well as the safety of MHT.
基金the result of PhD thesis approved in the Isfahan University of Medical Sciences(IUMS)to Vice Chancellery of Research of IUMS for the financial support, Research Project,#394774
文摘Estrogen hormones as a group of endocrine disruptive compounds （EDC） can interfere with endocrine system in humans and animals. The goal of this study was to investigate the elimination rate of Estrone （El）, 17β-estradiol （E2） and 17α-ethinyl estradiol （EE2） in Moving Bed Bioreactor （MBBR）. These analytes extracted by Dispersive Liquid-Liquid Microextraction （DLLME） technique, followed by derivatization, and detected by GC/MS. Estrogen removal efficiency in MBBR improved at high solid retention times （SRTs）, which notion is owing to development ofnitrification. Estrogenspecificremovalratewasbetween 0,22-1.45μg.（gVSS） 1.d -1 for natural and synthetic hormones. The adsorption rate was 0.9%-3.2% 0-1.3%, and 0.7%-5.7% for E1, E2, and EE2, respectively. In addition, the biodegradation rates were more than 95% for these compounds. These results illustrated that in MBBR, the hiodegradation and the adsorption to biomass are considered as two significant routes for elimination of estrogenic compounds. As a whole, the deterioration rate of estrogens enhanced by MBBR compared to other biological wastewater treatment processes such as conventional activated sludge.
基金supported in part by the Grant-in-Aid for Scientific Research (B) (No. 24360219)the Ministry of Education, Culture, Sports, Science and Technology (MEXT)Waseda University Grants for Special Research Project (No. 2013A-887)
文摘Treatments of estrogens such as Estrone （El）, Estradiol （E2） and Ethinylestradiol （EE2） were conducted using an electrolytic reactor equipped with multi-packed granular glassy carbon electrodes. Experimental results showed that El, E2 and EE2 were oxidized in the range of 0.45-0.85 V and were removed through electro-polymerization. Observed data from continuous experiments were in good agreement with calculated results by a mathematical model constructed based on mass transfer limitation. In continuous treatment of trace estrogens （1 μg/L）, 98% of El, E2 and EE2 were stably removed. At high loading rate （100 μg/L）, removal efficiency of E1 was kept around 74%-88% for 21 days, but removal efficiency reduced due to passivation of electrodes. However, removal efficiency was recovered after electrochemical regeneration of electrodes in presence of ozone. Electric energy consumption was observed in the range of 1-2 Wh/m3. From these results, we concluded that the present electrochemical process would be an alternative removal of estrogens.
文摘On study of the effects of estrogen deficiency on anxiety disorder by using ovariectomised animals, one discrepancy was the difference in behavioral testing delay following ovariectomy and the paradigms used. Thus, the aim of this study was to evaluate the anxiogenic effects of fourteen-day estrogen decline subsequent to ovariectomy on Wistar rats using EPM （elevated plus-maze） and open field tests. As results, fourteen days of estrogens decline has induced an increase of anxiety-related behaviour by a reduction of the percentage of the number of entries into the open arm （p 〈 0.01） and an increase of the percentage of the number of entries into the closed arm （/9 〈 0.01） during the elevated plus-maze test. This anxiety-like behaviour was confirmed on the open field test by a reduction of time spent in the centre of the arena （p 〈 0.05） as well as a reduction of crossing （p 〈 0.05） and an increase of the weight of faecal boli （p 〈 0.05） and grooming （p 〈 0.01）. Meanwhile, the administration of diazepam or estradiol valerate （1 mg/kg BW each） has corrected the anxious-like behaviour in both tests paradigms. These results suggest that fourteen days of estrogens decline was associated with an anxiety-related behaviour. This experimental model can constitute an excellent tool for the study of anxiolytic substances in menopause-related anxiety.
文摘Oral estrogens are directly associated with changes in plasma levels of coagulation proteins. Thus, the detection of any variation in protein concentrations due to estrogen contraceptives, by a simultaneous analysis of both coagulation proteins and estrogens, would be a very informative tool. In the present study, the merit of photo-selected reaction monitoring （SRM）, a new analytical tool, was evaluated towards estrogens detection in plasma. Then, SRM and photo-SRM detection modes were combined for the simultaneous analysis of estrogen molecules together with heparin co-factor and factor XIIa, two proteins involved in the coagulation cascade. This study shows that photo-SRM could open new multiplexed analytical routes.
文摘Highly sensitive voltammetric method for the determination of estrogens, based on the enhancement effect of cetyltrimethylammonium bromide (CTAB) has been described. In the presence of CTAB, the oxidation peak currents of estrogens (estradiol, estrone, estriol, estradiol valerate and diethylstilbestrol) as the carbon paste electrode (CPE) increased significantly after open-circuit accumulation. The peak current was proportional to the concentration of estradiol over the range from 5×10?9 to 2.5×10?6 mol·L?1. The detection limit was 8×10?10 mol·L?1 at 6 min of accumulation. The total amounts of estrogens in the blood serums were determined and the average recovery was 104.92%. Under the conditions used, the electrode process of estradiol was examined the mechanism for peak current enhancement was also discussed.
