Increased Estrogen Levels Research Articles

Local estrogen axis in the human bone microenvironment regulates estrogen\xa0receptor-positive\xa0breast cancer cells

BackgroundApproximately 70% of all breast cancers express the estrogen receptor, and are regulated by estrogen. While the ovaries are the primary source of estrogen in premenopausal women, most breast cancer is diagnosed following menopause, when systemic levels of this hormone decline. Estrogen production from androgen precursors is catalyzed by the aromatase enzyme. Although aromatase expression and local estrogen production in breast adipose tissue have been implicated in the development of primary breast cancer, the source of estrogen involved in the regulation of estrogen receptor-positive (ER+) metastatic breast cancer progression is less clear.MethodsBone is the most common distant site of breast cancer metastasis, particularly for ER+ breast cancers. We employed a co-culture model using trabecular bone tissues obtained from total hip replacement (THR) surgery specimens to study ER+ and estrogen receptor-negative (ER-) breast cancer cells within the human bone microenvironment. Luciferase-expressing ER+ (MCF-7, T-47D, ZR-75) and ER- (SK-BR-3, MDA-MB-231, MCF-10A) breast cancer cells were cultured directly on bone tissue fragments or in bone tissue-conditioned media, and monitored over time with bioluminescence imaging (BLI). Bone tissue-conditioned media were generated in the presence vs. absence of aromatase inhibitors, and testosterone. Bone tissue fragments were analyzed for aromatase expression by immunohistochemistry.ResultsER+ breast cancer cells were preferentially sustained in co-cultures with bone tissues and bone tissue-conditioned media relative to ER- cells. Bone fragments analyzed by immunohistochemistry revealed expression of the aromatase enzyme. Bone tissue-conditioned media generated in the presence of testosterone had increased estrogen levels and heightened capacity to stimulate ER+ breast cancer cell proliferation. Pretreatment of cultured bone tissues with aromatase inhibitors, which inhibited estrogen production, reduced the capacity of conditioned media to stimulate ER+ cell proliferation.ConclusionsThese results suggest that a local estrogen signaling axis regulates ER+ breast cancer cell viability and proliferation within the bone metastatic niche, and that aromatase inhibitors modulate this axis. Although endocrine therapies are highly effective in the treatment of ER+ breast cancer, resistance to these treatments reduces their efficacy. Characterization of estrogen signaling networks within the bone microenvironment will identify new strategies for combating metastatic progression and endocrine resistance.

Increased estrogen level can be associated with depression in males

BackgroundSeveral studies have shown a positive association between depression and obesity; however the underlying mechanisms are not fully understood. It is not known if this association is driven by altered sex hormone levels in men due to increased BMI. Patients and methodsData were obtained from the LIFE-Adult-Study, a population-based cohort study. A total of 3925 men (2244<60years and 1681>60years) were included into analyses. Associations between BMI, sex hormones and depressive symptomatology according to CES-D score were evaluated. ResultsObese men had compared to normal weight controls lower total testosterone (12.6±4.7 vs 19.4±5.5 nmol/L, p<0.001 in <60years, and 13.8±6.9 vs 18.3±5.9 nmol/L, p<0.001 in >60years group) and free testosterone (249.0±73.9 vs 337.2±82.0pmol/L, p<0.001, and 217.8±71.2 vs 263.4±72.2pmol/L, p<0.001), and increased estradiol in older group only (97.3±43.0 vs 82.3±34.2pmol/L, p<0.001 in obese). Men <60years old with depressive symptomatology had higher estradiol levels compared to those without depressive symptomatology (96.3±40.7 vs 84.4±36.6pmol/L, p<0.001), however no association with BMI was observed. ConclusionsSelected sex hormone parameters were significantly different in overweight and obese compared to normal weight males and certain differences could be seen between younger and older males. Depressive symptomatology was associated with increased estradiol levels in younger men, regardless of BMI.

Pemberian suplemen Swissoats A3® meningkatkan kadar hormon estrogen pada tikus (Rattus norvegicus) betina menopause galur Wistar

Abstract: Aging is a physiological process that occurs in all living creatures. Swissoats A3® is an anti-aging supplement that contains phytoestrogens. This study was aimed to prove that Swiss oats A3® supplementation could increase estrogen levels in menopausal female Wistar rats (Rattus norvegicus). This was an experimental study with a completely randomized pretest-posttest control group design. Subjects were 20 menopausal female rats (Rattus norvegicus), Wistar strain, healthy, aged 15-16 months, weighing 200 g, divided into 2 groups: the control group (P0), treated with distilled water for 21 days and the treatment group (P1), treated with Swissoats A3® of 34.2 mg/rat/day for 21 days. Before and after 21 days of treatment, 1 ml venous blood was drawn through the medial canthus of orbital sinus using microcapillary tube and the estrogen levels were meassured by using indirect ELISA method. The results showed that before treatment, the mean estrogen level in P0 group was 14.96±2.0468 pg/ml and in P1 group was 14.21±2.3905 pg/ml (P &gt; 0.05). Meanwhile, after 21-day treatment, the mean estrogen level in P0 group was 15.07±1.8851 pg/ml, whereas in P1 group was 28.33±3.2052 pg/ml (P &lt; 0.01). The analysis showed that the Swissoats A3® could elevate the estrogen levels significantly (P &lt; 0.01) in group P1 (2.3905±14.21 vs 28.33±3.205). Conclusion: Swissoats A3® supplementation could increase the estrogen levels in menopausal female Wistar rats (Rattus norvegicus).Keywords: Swiss oats A3®, estrogen, female Wistar rats, menopauseAbstrak: Penuaan (aging) merupakan suatu proses fisiologik yang dialami oleh seluruh mahluk hidup. Swissoats A3® merupakan suplemen anti-aging yang mengandung fitoestrogen. Penelitian ini bertujuan untuk membuktikan bahwa pemberian suplemen Swissoats A3® dapat meningkatkan kadar estrogen pada tikus (Rattus norvegicus) betina menopause galur Wistar. Jenis penelitian ialah eksperimental dengan randomized pretest-posttest control group design. Subjek penelitian ialah 20 ekor tikus putih betina (Rattus norvegicus) galur Wistar, sehat, menopause, umur 15-16 bulan, berat badan 200 gr. Tikus dibagi menjadi 2 kelompok yaitu kelompok kontrol (P0) yang diberikan aquadest secara sonde selama 21 hari dan kelompok perlakuan yang diberikan suplemen Swissoats A3® dosis 34,2mg/ekor/hari secara sonde selama 21 hari. Sebelum dan sesudah 21 hari perlakuan, darah vena diambil melalui medial canthus sinus orbitalis sekitar 1 ml dengan menggunakan tabung mikrokapiler dan dilakukan pemeriksaan kadar estrogen menggunakan metode indirect ELISA. Hasil penelitian menunjukkan bahwa sebelum perlakuan, rerata kadar estrogen kelompok P0 14,96±2,0468 pg/ml dan kelompok P1 14,21±2,3905 pg/ml (P &gt; 0,05). Setelah perlakuan selama 21 hari, rerata kadar estrogen kelompok P0 15,07±1,8851 pg/ml dan kelompok P1 28,33±3,2052 pg/ml (P &lt; 0,01). Analisis efek perlakuan menunjukkan terjadinya peningkatan kadar hormon estrogen yang sangat bermakna (P &lt; 0,01) pada kelompok P1 (14,21±2,3905 vs 28,33±3,205). Simpulan: Swissoats A3® dapat meningkatkan kadar estrogen pada tikus (Rattus norvegicus) betina menopause galur wistar.Kata kunci: Swissoats A3®, estrogen, tikus wistar betina, menopause

Metabolism of sex steroids is influenced by acquired adiposity—A study of young adult male monozygotic twin pairs

Obesity and ageing are associated with lower serum testosterone levels in men. How fat distribution or adipose tissue metabolism, independent of genetic factors and age, are related to sex steroid metabolism is less clear. We studied the associations between adiposity and serum sex hormone concentrations, and mRNA expression of genes regulating sex hormone metabolism in adipose tissue in young adult male monozygotic (MZ) twin pairs. The subjects [n=18 pairs; mean age, 32 years; individual body mass indexes (BMIs) 22–36kg/m2] included 9 male MZ twin pairs discordant for BMI [intra-pair difference (Δ) in BMI ≥3kg/m2]. Sex steroid concentrations were determined by liquid chromatography–tandem mass spectrometry, body composition by dual-energy X-ray absorptiometry and magnetic resonance imaging, and mRNA expressions from subcutaneous adipose tissue by Affymetrix. In BMI-discordant pairs (mean ΔBMI=5.9kg/m2), serum dihydrotestosterone (DHT) was lower [mean 1.9 (SD 0.7) vs. 2.4 (1.0) nmol/l, P=0.040] and mRNA expressions of DHT-inactivating AKR1C2 (P=0.021) and cortisol-producing HSD11B1 (P=0.008) higher in the heavier compared to the leaner co-twins. Serum free 17β-estradiol (E2) was higher [2.3 (0.5) vs. 1.9 (0.5) pmol/l, P=0.028], and in all twin pairs, serum E2 and estrone concentrations were higher in the heavier than in the leaner co-twins [107 (28) vs. 90 (22) pmol/l, P=0.006; and 123 (43) vs. 105 (27) pmol/l, P=0.025]. Within all twin pairs, i.e. independent of genetic effects and age, 1) the amount of subcutaneous fat inversely correlated with serum total and free testosterone, DHT, and sex hormone-binding globulin (SHBG) concentrations (P<0.01 for all), 2) intra-abdominal fat with total testosterone and SHBG (P<0.05), and 3) liver fat with SHBG (P=0.006). Also, 4) general and intra-abdominal adiposity correlated positively with mRNA expressions of AKR1C2, HSD11B1, and aromatase in adipose tissue (P<0.05). In conclusion, acquired adiposity was associated with decreased serum DHT and increased estrogen concentrations, independent of genetic factors and age. The reduction of DHT could be linked to its increased degradation (by AKR1C2 and HSD11B1) and increased estrogen levels to increased adiposity-related expression of aromatase in adipose tissue.

Maternal exposure to polybrominated diphenyl ether (BDE-209) during lactation affects germ cell survival with altered testicular glucose homeostasis and oxidative status through down-regulation of Cx43 and p27Kip1 in prepubertal mice offspring.

BDE-209, a congener of polybrominated diphenyl ethers (PBDEs), is mainly used as flame retardant and accounts for over 82% of total PBDE usage. PBDEs have recently been detected in human milk and cord blood. BDE-209 possesses weak estrogenic/anti-estrogenic properties and evokes hyperglycemia through impaired glucose homeostasis in rat liver. However, little is known of the effect of lactational exposure to BDE-209 on germ cell survival in relation to testicular glucose homeostasis, estradiol and oxidative status during prepubertal period. The present study, therefore, evaluated the effect of maternal exposure to BDE-209 during lactation on above-mentioned parameters with reference to Cx43 and p27Kip1 in prepubertal Parkes (P) mice offspring. Lactating female P mice were orally gavaged with 500, and 700mg/kg body weight of BDE-209 in corn oil from postnatal day (PND) 0 to PND 28; male pups were euthanized at PND 21 and 28. Maternal exposure to BDE-209 during lactation increased germ cell apoptosis with altered expressions of various cell survival and apoptotic markers along with decreased expression of Cx43 and p27Kip1 in prepubertal mice offspring. Testicular glucose and lactate concentrations were markedly reduced in these pups with down-regulation in GLUT3 and GLUT8 expressions and decreased LDH activity. Rise in oxidative stress in testes with increased estrogen level in these pups was also noted. In conclusion, our results suggest that maternal BDE-209 exposure during lactation affects germ cell survival with altered testicular glucose homeostasis and oxidative status through down-regulation of Cx43 and p27Kip1 in prepubertal mice offspring.

Safety of a C1-inhibitor concentrate in pregnant women with hereditary angioedema

Increased estrogen levels during pregnancy can exacerbate hereditary angioedema (HAE), yet disease and treatment ramifications remain poorly studied in pregnant women. Data from the international Berinert Patient Registry were used to evaluate outcomes of pregnancies exposed to plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH) during routine HAE management. This observational registry, conducted between 2010 and 2014 at 30 U.S. and 7 European sites, gathered data on 318 subjects and 15,000 pnfC1-INH infusions. Whenever possible, the subjects who used pnfC1-INH during pregnancy were followed up to term to assess neonatal outcomes and to collect maternal adverse events (AE) that occurred up to 1 month after pnfC1-INH administration. The registry data base included 11 pregnancies in 10 subjects who used pnfC1-INH for HAE attack treatment and/or prophylaxis (>261 doses during pregnancy). Eight pregnancies concluded in the birth of a healthy baby. Of the remaining three pregnancies: one was voluntarily terminated at 9 weeks of gestation; a second ended as a first-trimester spontaneous abortion 1 week after the subject's most recent pnfC1-INH infusion and was considered unrelated to pnf-C1INH treatment; and the third occurred in a subject who exited the registry approximately 2 months before her due date, with no further follow up. As assessed for 30 days after each pnfC1-INH infusion, there were no AEs that were considered related to pnfC1-INH therapy. Administration of pnfC1-INH during pregnancy was generally safe and not associated with any treatment-related AEs. In all registry pregnancies followed up to term, the birth of a healthy baby was reported.

Role of estrogen receptor signaling in skeletal response to leptin in female ob/ob mice.

Leptin, critical in regulation of energy metabolism, is also important for normal bone growth, maturation and turnover. Compared to wild type (WT) mice, bone mass is lower in leptin-deficient ob/ob mice. Osteopenia in growing ob/ob mice is due to decreased bone accrual, and is associated with reduced longitudinal bone growth, impaired cancellous bone maturation and increased marrow adipose tissue (MAT). However, leptin deficiency also results in gonadal dysfunction, disrupting production of gonadal hormones which regulate bone growth and turnover. The present study evaluated the role of increased estrogen in mediating the effects of leptin on bone in ob/ob mice. Three-month-old female ob/ob mice were randomized into one of the 3 groups: (1) ob/ob + vehicle (veh), (2) ob/ob + leptin (leptin) or (3) ob/ob + leptin and the potent estrogen receptor antagonist ICI 182,780 (leptin + ICI). Age-matched WT mice received vehicle. Leptin (40 µg/mouse, daily) and ICI (10 µg/mouse, 2×/week) were administered by subcutaneous injection for 1 month and bone analyzed by X-ray absorptiometry, microcomputed tomography and static and dynamic histomorphometry. Uterine weight did not differ between ob/ob mice and ob/ob mice receiving leptin + ICI, indicating that ICI successfully blocked the uterine response to leptin-induced increases in estrogen levels. Compared to leptin-treated ob/ob mice, ob/ob mice receiving leptin + ICI had lower uterine weight; did not differ in weight loss, MAT or bone formation rate; and had higher longitudinal bone growth rate and cancellous bone volume fraction. We conclude that increased estrogen signaling following leptin treatment is dispensable for the positive actions of leptin on bone and may attenuate leptin-induced bone growth.

Ovarian hormones and obesity.

Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE. Articles in English indexed in PubMed through January 2016 were searched using keywords related to: (i) reproductive hormones, (ii) weight regulation and (iii) central nervous system. We sought to identify emerging research foci with clinical translational potential rather than to provide a comprehensive review. We find that estrogens play a leading role in the causes and consequences of female obesity. With respect to adiposity, estrogens synergize with AT genes to increase gluteofemoral subcutaneous AT mass and decrease central AT mass in reproductive-age women, which leads to protective cardiometabolic effects. Loss of estrogens after menopause, independent of aging, increases total AT mass and decreases lean body mass, so that there is little net effect on body weight. Menopause also partially reverses women's protective AT distribution. These effects can be counteracted by estrogen treatment. With respect to eating, increasing estrogen levels progressively decrease eating during the follicular and peri-ovulatory phases of the menstrual cycle. Progestin levels are associated with eating during the luteal phase, but there does not appear to be a causal relationship. Progestins may increase binge eating and eating stimulated by negative emotional states during the luteal phase. Pre-clinical research indicates that one mechanism for the pre-ovulatory decrease in eating is a central action of estrogens to increase the satiating potency of the gastrointestinal hormone cholecystokinin. Another mechanism involves a decrease in the preference for sweet foods during the follicular phase. Genetic defects in brain α-melanocycte-stimulating hormone-melanocortin receptor (melanocortin 4 receptor, MC4R) signaling lead to a syndrome of overeating and obesity that is particularly pronounced in women and in female animals. The syndrome appears around puberty in mice with genetic deletions of MC4R, suggesting a role of ovarian hormones. Emerging functional brain-imaging data indicates that fluctuations in ovarian hormones affect eating by influencing striatal dopaminergic processing of flavor hedonics and lateral prefrontal cortex processing of cognitive inhibitory controls of eating. There is a dearth of research on the neuroendocrine control of eating after menopause. There is also comparatively little research on the effects of ovarian hormones on EE, although changes in ovarian hormone levels during the menstrual cycle do affect resting EE. The markedly greater obesity burden in women makes understanding the diverse effects of ovarian hormones on eating, EE and body adiposity urgent research challenges. A variety of research modalities can be used to investigate these effects in women, and most of the mechanisms reviewed are accessible in animal models. Therefore, human and translational research on the roles of ovarian hormones in women's obesity and its causes should be intensified to gain further mechanistic insights that may ultimately be translated into novel anti-obesity therapies and thereby improve women's health.

English

In Pakistan, the most favorable consumption in meat nowadays is chicken. The inclination of the dietary pattern to chicken meat more than red meat may be because of its better taste, easy availability and low cost. At the same time, there is an increase in prevalence of polycystic ovaries 5 to 10% in Pakistan. The present study was designed to investigate the effects of the chicken feed and chicken meat on the growth, body weight and the serum estrogen levels in the female albino wistar rats. Seventy five female albino wistar rats were used in the experiment, randomly assigned to three groups (n=25); control rats fed on chow, chicken feed treated rats and chicken meat treated rats for a period of 6 weeks. Body weight and serum estrogen levels were estimated before and after the treatment whereas growth rates were calculated after the experiment. A significant increase in growth rate and serum estrogen levels (P&lt;0.05) was observed in both test groups as compared to control group. This increase was however more in chicken meat (III) as compared to chicken feed (II) group (p &lt;0.05). It is therefore suggested that the potential cause of weight gain, growth and increased estrogen levels may be result of dietary inclination of people towards chicken meat leading to polycystic ovaries (PCOs) and infertiity. &nbsp; Key words: Chicken feed, chicken meat, estrogens, growth rate.

Metabolomics study on primary dysmenorrhea patients during the luteal regression stage based on ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry

Primary dysmenorrhea (PD) is a common gynecological disorder which, while not life-threatening, severely affects the quality of life of women. Most patients with PD suffer ovarian hormone imbalances caused by uterine contraction, which results in dysmenorrhea. PD patients may also suffer from increases in estrogen levels caused by increased levels of prostaglandin synthesis and release during luteal regression and early menstruation. Although PD pathogenesis has been previously reported on, these studies only examined the menstrual period and neglected the importance of the luteal regression stage. Therefore, the present study used urine metabolomics to examine changes in endogenous substances and detect urine biomarkers for PD during luteal regression. Ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry was used to create metabolomic profiles for 36 patients with PD and 27 healthy controls. Principal component analysis and partial least squares discriminate analysis were used to investigate the metabolic alterations associated with PD. Ten biomarkers for PD were identified, including ornithine, dihydrocortisol, histidine, citrulline, sphinganine, phytosphingosine, progesterone, 17-hydroxyprogesterone, androstenedione, and 15-keto-prostaglandin F2α. The specificity and sensitivity of these biomarkers was assessed based on the area under the curve of receiver operator characteristic curves, which can be used to distinguish patients with PD from healthy controls. These results provide novel targets for the treatment of PD.

Tomato (Lycopersicum commune) Juice and Physical Exercise Increase Number of Neurons and ERβ expression in Post-Ovariectomy Rats Brain

Background: Estrogen deficiency condition can degrade the quality of life, decline in cognitive function will be more severe trough age. Phytoestrogen compounds can be found in pegaga leaf extract, tomatoes, and papaya is an easy and inexpensive way to increase estrogen levels in post menopause women through extra gonadal estrogen induction. Therefore, the aims of this study were to examine the effect of tomato juice, physical exercise, and combination of these treatments on promoting neurons and ER? expression in somatosensory cortex that contribute to cognitive function of post-ovariectomy rats. Method: Twenty-eight female healthy Wistar rats (Rattus novergicus), 8-10 weeks old, from Laboratory of Biochemistry, Faculty of Medicine Airlangga University include in this experiment. The animals were housed in the animal-care facility with ad libitum food and water. The temperatur was maintained at 18°C-24°C. The treatments were done 2 weeks after ovariectomy. Tomato were made in Laboratory of Pharmacognocy and Phytochemistry, Faculty of Pharmacy, Airlangga University, from inner part of the tomato fruits (mucous like substance) with freeze dry method (-40°C). Results: The weight of white rat Rattus norvegicus post ovariectomy in this study was between 133-170 gram with a mean weight 154.32 ± 9.72 gram. Hematoxylin/eosin staining showed neuronal deficit in the control rats brain. In figure 1, the tomato group showed the largest of neurons number (145.43 ± 17.728), followed the combination group (140.57 ± 22.449), the exercise group (136.86 ± 23.104) and the smallest number in the control group (96.43± 28.965). Four weeks after treatments the number of neurons increased significant in the tomato group (p=0.001), exercise group (p=0.004) and combination group (p=0.002) from the control group. This study showed no significant different between tomato and exercise group (p=0.500), tomato and combination group (p=0.701) and between exercise and combination group (p=0.769). Conclusions: In conclusion, our data demonstrated that post ovariectomy rats showed deficit numbers of neurons and decreased ER? in the somatosensory cortex. Treatment with physical exercise, tomato juice, and combination of these treatments increased the number of neurons and ER? expression in the somatosensory cortex.

Association of infertility and fertility treatment with mammographic density in a large screening-based cohort of women: a cross-sectional study.

BackgroundOvarian stimulation drugs, in particular hormonal agents used for controlled ovarian stimulation (COS) required to perform in vitro fertilization, increase estrogen and progesterone levels and have therefore been suspected to influence breast cancer risk. This study aims to investigate whether infertility and hormonal fertility treatment influences mammographic density, a strong hormone-responsive risk factor for breast cancer.MethodsCross-sectional study including 43,313 women recruited to the Karolinska Mammography Project between 2010 and 2013. Among women who reported having had infertility, 1576 had gone through COS, 1429 had had hormonal stimulation without COS and 5958 had not received any hormonal fertility treatment. Percent and absolute mammographic densities were obtained using the volumetric method Volpara™. Associations with mammographic density were assessed using multivariable generalized linear models, estimating mean differences (MD) with 95 % confidence intervals (CI).ResultsAfter multivariable adjustment, women with a history of infertility had 1.53 cm3 higher absolute dense volume compared to non-infertile women (95 % CI: 0.70 to 2.35). Among infertile women, only those who had gone through COS treatment had a higher absolute dense volume than those who had not received any hormone treatment (adjusted MD 3.22, 95 % CI: 1.10 to 5.33). No clear associations were observed between infertility, fertility treatment and percent volumetric density.ConclusionsOverall, women reporting infertility had more dense tissue in the breast. The higher absolute dense volume in women treated with COS may indicate a treatment effect, although part of the association might also be due to the underlying infertility. Continued monitoring of cancer risk in infertile women, especially those who undergo COS, is warranted.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0693-5) contains supplementary material, which is available to authorized users.

URINE EXCRETION STUDY OF TAMOXIFEN METABOLITE, 3-HYDROXY-4-METHOHY TAMOXIFEN BY GC-MS

Background; Tamoxifen, is a first-generation selective estrogen receptor modulator which is widely used for adjuvant breast cancer therapy. Tamoxifen metabolite completely bind to estrogen receptor on tumors as well as other tissues and target a nuclear complex that decreases DNA synthesis and inhibits estrogen effects. But these Selective Estrogen Receptor Modulators (SERMs) are classified as Prohibited substances according to the list of forbidden substances in sports by the World Anti-Doping Agency(WADA) In sports male athletes use tamoxifen in fighting against increase of estrogen level in the body, breast swelling , gynecomastia and fat forming a pear-silhouette very successfully. Aim; In the present study  Tamoxifen was investigated carefully by administering to a Healthy volunteer . Material And Method; Urine samples are collected at different hours  from 1st day to 5th day and analyzed by GC-MS. Result; It was  found that Tamoxifen is rapidly metabolized in to their metabolite 3-hydrohy-4-methoxy Tamoxifen. Urinary extracts were analyzed by Gas Chromatography-Mass spectrometric Detector by using Selective ion modulator(SIM) and targeted GC-MS techniques with accurate mass. By the GC-MS study it is observed that 3-hydroxy-4-methoxy Tamoxifen metabolite gives two neutral loss m/z value at 58 & 72, but m/z value 58 shows more abundance than 72m/z value, hence it was selected as the marker m/z value to check the presence of metabolite in urine. Conclusion; After oral administration, Tamoxifen metabolite can be detected in to their maximum period up to 5 days.Â

Human Adenomyosis Endometrium Stromal Cells Secreting More Nerve Growth Factor: Impact and Effect.

Abnormal expression of nerve growth factor (NGF) was found in adenomyosis (AM). We collected AM foci from patients and eutopic endometrium from non-AM controls. Endometrium stromal cells (ESCs) were cultured. Different levels of 17β-estradiol, tumor necrosis factor (TNF), CoCl2, and H2O2 were added to the culture system separately, then the expression level of NGF in ESCs was detected. After adding different levels of NGF, the proliferation and apoptosis of ESCs and aromatase expression were detected. We found that 17β-estradiol promoted NGF production in AM ESCs but not in control ESCs; TNF promoted NGF production in both AM and control ESCs; and CoCl2 inhibited NGF production in control ESCs, but had no effect in AM ESCs. Nerve growth factor promoted the proliferation and synthesis of aromatase in AM ESCs. In conclusion, locally increased estrogen levels and inflammation may cause increased NGF production in the uterus of patients with AM. Nerve growth factor stimulated the proliferation and increased aromatase expression of ESCs from AM foci, suggesting NGF might contribute to the pathology and etiology of AM.

Abstract 5042: Dynamic transcriptional regulation of ERα targets in prostate cancer

Abstract Introduction: Prostate cancer is the second most common cause of cancer death in American men. Prostate cancer is mainly an androgen receptor regulated disease, however estrogen signaling is also important in prostate physiology and development particularly in aging men as decreasing testosterone is accompanied by increasing estrogen levels. Further, estrogen signaling through estrogen receptor alpha (ERα) has been implicated in prostate cancer progression, and ERα expression increases in high grade tumors, however its precise role remains unclear. Thus far there have been no systematic approaches to assay ERα transcriptional regulation in prostate cancer, and in this study we aim to determine the role of ERα in prostate cancer by identifying direct ERα target genes. Methods: ERα recruitment profile was assayed by ChIP-Seq in both NCI-H660 and ERα overexpressing VCaP cells in response to estrogen treatment. ERα transcriptional regulation of target genes was examined utilizing RNA-Seq in VCaP cells with and without ERα overexpression. Candidate gene expression was assayed via qPCR in prostate cancer cell lines, and by RNA-Seq in a 126 sample prostate cancer patient cohort. Results: In order to delineate the role of ERα in prostate cancer we integrated RNA- and ChIP-Seq datasets from two different cell lines in response to ERα overexpression and estrogen treatment. In doing so we identified an ERα signature comprising multiple genes that were significantly up or down-regulated (&amp;gt; 5-fold) and had an ERα binding site near the gene promoter. Many of these ERα target genes have been previously identified as oncogenes or tumor suppressors, and they include members several key pathways including PI3 kinase signaling and cytoskeleton maintenance. Expression of these target genes was queried in multiple prostate cancer cell lines, and interestingly ERα binding sites and estrogen regulation were cell line specific in both androgen receptor positive and negative lines. Further, significant differences in target gene expression were demonstrated between benign prostate and prostate adenocarcinoma (PCa), and/or between PCa and castration-resistant prostate cancer (CRPC) or neuroendocrine prostate cancer (NEPC). Combinatorial targeting of both ERα and PI3K signaling proved beneficial for prostate cancer. Conclusion: These results demonstrate that estrogen regulates a distinct set of genes in prostate cancer in a direct genomic fashion, including several components of the PI3K pathway. They also support the hypothesis that this ERα signature is dynamic and changes during the course of prostate cancer progression to CRPC and NEPC. Further validation of the pathways involved is necessary, however these findings may lead to the discovery of novel co-targeting treatment strategies and/or prostate cancer biomarkers, and assessment of ERα signaling may help predict a subclass of prostate cancer patients that are likely to respond to PI3K inhibition. Citation Format: Kellie Cotter, Dimple Chakravarty, Andrea Sboner, Mark A. Rubin. Dynamic transcriptional regulation of ERα targets in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5042. doi:10.1158/1538-7445.AM2015-5042

TRIGLYCERIDE LEVELS AS A RISK FACTOR DURING PREGNANCY; BIOLOGICAL MODELING; SYSTEMATIC REVIEW

introduction: Some of the diseases that can appear in pregnancy (gestational diabetes, hypertension and preeclampsia) are being associated with an increased risk of heart throughout life diseases. This should be present in future assessments of the health of women. One of the most important biomarkers in cardiovascular diseases is the triglyceride level, and that undergoes a significant change during pregnancy. the objective of this review is to analyze the studies that have investigated triglyceride levels during pregnancy as a risk factor for cardiovascular disease in the last weeks of pregnancy and childbirth. a systematic search was made and 14 specific articles on the subject were selected following the PRISMA guidelines. in normal pregnancy decreased the level of lipids in the first weeks, followed by a gradual increase. Especially high from the 12th week of gestation. This increase in plasma levels of circulating lipids occurs linearly, reaching a peak a few days before delivery. This increase results because of the increased estrogen levels and insulin resistance. It has also been associated with prolactin levels. through this review, it has been able to demonstrate the relationship of elevated triglycerides some pathologies or more frequent changes in risk pregnancies, in which a significantly higher elevation occurs compared to normal pregnancies. It is in this context that the biological modeling may be particularly important, facilitating the creation of models and percentile curves applicable to the population, and allow monitoring of changes in triglycerides, which end up pointing situations passing be predictors of a potentially pathological situation. Thus, appropriate interventions would be carried rafter more briefly, and see so favored adequate primary prevention.

The antipsychotic drug sulpiride induces insulin intolerance but does not affect body weight in adult male mice

Research studies have shown that chronic administration of some antipsychotic drugs induces obesity in female but not in male. To explore the mechanisms involved in this effect, we administrated the dopamine antagonist sulpiride (40 mg/kg) or vehicle intraperitoneally to adult male mice during 45 days and then the glucose tolerance and serum levels of insulin, serum, and testicular testosterone and prolactin, and blood estrogen levels were evaluated. Chronic sulpiride administration did not affect body weight. However, prolactin levels and the area under the glucose and insulin curves were significantly elevated. Sulpiride significantly decreased testosterone and increased estrogen levels (p < 0.05). After prolonged administration, sulpiride did not affect body weight, so this lack of effect may be related to the impairment of insulin sensitivity which prevents body weight gain and deals with other effects of sulpiride that cause adiposity promotion such as hyperprolactinemia. Future studies must evaluate other neurotransmitters involved in food intake regulation such as histamine and serotonin.

Influence of physiological changes in endogenous estrogen on circulating PCSK9 and LDL cholesterol

Pharmacologically increased estrogen levels have been shown to lower hepatic and plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels in animals and humans. We hypothesized that physiological changes in estrogen levels influence circulating PCSK9, thereby contributing to the known wide inter-individual variation in its plasma levels, as well as to the established increase in LDL cholesterol (LDL-C) with normal aging. Circulating PCSK9, estradiol, and other metabolic factors were determined in fasting samples from 206 female and 189 male healthy volunteers (age 20–85 years), The mean levels of PCSK9 were 10% higher in females than in males (P

Vulvovaginal candidiasis in pregnancy.

Prevalence studies indicate that Candida species colonize the vagina in at least 20% of all women, rising to 30% in pregnancy. Although, some studies concluded that pregnant women were more likely to have symptomatic vaginal infections caused by Candida, yet other studies found a high prevalence of asymptomatic infection only during pregnancy. Most episodes of symptomatic vulvovaginal candidiasis (VVC) occur during the second and third trimesters. The increased risk of VVC in pregnancy is likely sustained by pregnancy-related factors, such as immunologic alterations, increased estrogen levels, and increased vaginal glycogen production. Although evidence is incomplete, there is some emerging data which suggests that candidiasis in pregnancy may be associated with increased risk of pregnancy complications, such as premature rupture of membranes, preterm labor, chorioamnionitis, and congenital cutaneous candidiasis. In contrast to nonpregnant women, there are no formal studies, evaluating the use of long-term suppressive maintenance oral azoles in the treatment of recurrent VVC (RVVC) in pregnancy. Most clinicians do not offer suppressive therapy in pregnancy and prefer to treat individual symptomatic episodes only utilizing a topical imidazole vaginally for 7days to minimize systemic exposure to medications.

Estrogen inhibits lysyl oxidase and decreases mechanical function in engineered ligaments.

Women are more likely to suffer an anterior cruciate ligament (ACL) rupture than men, and the incidence of ACL rupture in women rises with increasing estrogen levels. We used an engineered ligament model to determine how an acute rise in estrogen decreases the mechanical properties of ligaments. Using fibroblasts isolated from human ACLs from male or female donors, we engineered ligaments and determined that ligaments made from female ACL cells had more collagen and were equal in strength to those made from male ACL cells. We then treated engineered ligaments for 14 days with low (5 pg/ml), medium (50 pg/ml), or high (500 pg/ml) estrogen, corresponding to the range of in vivo serum estrogen concentrations and found that collagen within the grafts increased without a commensurate increase in mechanical strength. Mimicking the menstrual cycle, with 12 days of low estrogen followed by 2 days of physiologically high estrogen, resulted in a decrease in engineered ligament mechanical function with no change in the amount of collagen in the graft. The decrease in mechanical stiffness corresponded with a 61.7 and 76.9% decrease in the activity of collagen cross-linker lysyl oxidase with 24 and 48 h of high estrogen, respectively. Similarly, grafts treated with the lysyl oxidase inhibitor β-aminoproprionitrile (BAPN) for 24 h showed a significant decrease in ligament mechanical strength [control (CON) = 1.58 ± 0.06 N; BAPN = 1.06 ± 0.13 N] and stiffness (CON = 7.7 ± 0.46 MPa; BAPN = 6.1 ± 0.71 MPa) without changing overall collagen levels (CON = 396 ± 11.5 μg; BAPN = 382 ± 11.6 μg). Together, these data suggest that the rise in estrogen during the follicular phase decreases lysyl oxidase activity in our engineered ligament model and if this occurs in vivo may decrease the stiffness of ligaments and contribute to the elevated rate of ACL rupture in women.