Dietary Estrogens Research Articles

The effect of dietary estrogens and acupuncture combined with exercise or exercise alone on bone mineral density in adolescent female athletes suffering from the female athlete triad: A randomized clinical trial

The aim of this study was to investigate the effect of dietary estrogens and acupuncture combined with exercise or exercise alone on bone mineral density in adolescent female athletes suffering from the female athlete triad. A single blind randomized controlled trial was carried out. A total of 44 girls (in adolescence age) diagnosed with low BMD (bone mineral density) resulting from female athlete triad participated in this study. They were divided into three equal groups (group A, B and C). Group A (n = 15) received estrogen from dietary origin in the form of soy milk or soybeans daily in the breakfast combined with weight bearing (WB) exercises. Group B (n = 15) received acupuncture therapy on the acupoints responsible for bone density according to Chinese meridians combined with WB exercises, while group C (n = 14) received WB exercises only. The program was given for 45-60 min/session, three sessions per week for 24 weeks. Z score by Dual-energy X-ray absorptiometry (DEXA) for bone mineral density (BMD) assessment and estradiol 2 (E2) for measuring serum estrogen in blood were measured before treatment and after 24 weeks of treatment. The study groups were comparable on all outcome measures. Within-group comparison showed statistically significant improvements in all measured variables (p < 0.05). Further, between-groups comparison revealed statistically significantly higher improvements in the measured variables, in favor of group B (p < 0.05). The acupuncture sessions combined with WB exercises may be effective in improving bone mineral density in female athlete triad, rather than diet modification by adding soy phytoestrogen in meals beside exercise or exercise alone.

Beneficiary and Adverse Effects of Phytoestrogens: A Potential Constituent of Plant-based Diet.

Phytoestrogens are non-endocrine, non-steroidal secondary derivatives of plants and consumed through a plant-based diet also named as "dietary estrogens". The major sources of phytoestrogens are soy and soy-based foods, flaxseed, chickpeas, green beans, dairy products, etc. The dietary inclusion of phytoestrogen based foods plays a crucial role in the maintenance of metabolic syndrome cluster, including obesity, diabetes, blood pressure, cancer, inflammation, cardiovascular diseases, postmenopausal ailments and their complications. In recent days, phytoestrogens are the preferred molecules for hormone replacement therapy. On the other hand, they act as endocrine disruptors via estrogen receptor-mediated pathways. These effects are not restricted to adult males or females and identified even in development. Since phytoestrogenic occurrence is high at daily meals for most people worldwide, they focused to study for its beneficiary effects towards developing pharmaceutical drugs for treating various metabolic disorders by observing endocrine disruption. The present review emphasizes the pros and cons of phytoestrogens on human health, which may help to direct the pharmaceutical industry to produce various phytoestrongen based drugs against various metabolic disorders.

Simultaneous determination of formononetin, biochanin A and their active metabolites in human breast milk, saliva and urine using salting-out assisted liquid-liquid extraction and ultra high performance liquid chromatography-electrospray ionization tandem mass spectrum

Isoflavonoid phytoestrogens, referred as “dietary estrogens” are widely distributed in the plant kingdom. Formononetin, biochanin A and their active metabolites daidzein and genistein are known to be the most potent among other isoflavonoid phytoestrogens. Thus there is a growing need to determine accurately their concentration in different biological fluids. In the present work, a sensitive analytical method was developed for the quantitative determination of these compounds in human breast milk, saliva and urine. The glycoside conjugates of these compounds were enzymatically hydrolysis prior to salting-out assisted liquid-liquid extraction. Quantitative analysis was done by ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. The obtained results showed high correlation coefficients (r2 > 0.998) for the linear range established for formononetine, biochanin A, daidzein and genistein. The limits of detection (LODs) and low limits of quantitation (LLOQs) were in the ranges of 0.05–1.0 ng/mL and 1.0–4.0 ng/mL for all analytes in human biological fluids, respectively. The average recoveries ranged from 83.29% to 115.24% for the analytes with relative standard deviation (n = 5) values from 1.84% to 9.75% in samples. Both intra-day and inter-day precisions and accuracy were found to be within 12.53% and ± 12.92% respectively. Under different conditions of stability, the concentrations for four isoflavonoid phytoestrogens deviated within ±12.87% of norminal values. The developed method was successfully validated and applied to human breast milk, saliva and urine. The average concentrations of daidzein and genistein found in breast milk, saliva and urine samples ranged from 0 to 104.2 µg/kg, 18.17 to 786.0 µg/kg, 0 to 10974 µg/kg, respectively. Their presence in breast milk samples shows exposure of breast-fed baby to isoflavones. It also allows for the rapid screening of human biological fluids when testing for formononetin, biochanin A, daidzein and genistein production status in human.

Syringaresinol as a novel androgen receptor antagonist against wild and mutant androgen receptors for the treatment of castration-resistant prostate cancer: molecular docking, in-vitro and molecular dynamics study

Phytoestrogens are dietary estrogens having similar structure as of estrogen. Some of these phytoestrogens are androgen receptor (AR) antagonists and exhibit preventive role in the prostate cancer. However, in androgen-independent prostate cancer (AIPC) the ARs were mutated (T877A, W741L, F876L, etc.) and these mutant ARs convert the antagonist to agonist. Our aim in this study is to find phytoestrogens that could function as an antagonist with wild and mutant ARs. The phytoestrogens were analyzed for binding affinity with wild and mutant ARs in agonist and antagonist conformations. The point mutations were carried out using Chimera. The antagonist AR conformation was modeled using Modeller. We hypothesize that the compounds having binding affinity with agonist AR conformation could not function as a full or pure antagonist. Most of the phytoestrogens have binding affinity with agonist AR conformation contradicting previous results. For example, genistein which is a widely studied isoflavone has known AR antagonist property. However, in our study, it had good binding affinity with agonist AR conformation. Hence, to confirm our hypothesis, we tested genistein in LNCaP (T877A mutant AR) cells by qPCR studies. The genistein functioned as an antagonist only in the presence of an androgen indicting a partial agonist type of activity. The in-vitro results supported our docking hypothesis. We applied this principle and found syringaresinol could function as an antagonist with wild and mutated ARs. Further, we carried out molecular dynamics for the hit molecule to confirm its antagonist binding mode with mutant AR.Communicated by Ramaswamy H. Sarma

Effect of Both Bisphenol - A and Liquorice on Some Sexual Hormones in Male Albino Rats and Illustration of the Effect of Stem Cell Enhancer on Their Actions

Background: Xenoestrogens are a type of xenohormone that imitates estrogen. They can be either synthetic or natural chemical compounds. Synthetic xenoestrogens include some widely used industrial compounds, such as PCBs, bisphenol A (BPA) and phthalates. "Dietary estrogen" is also called phytoestrogen, which is a plantderived xenoestrogen not generated within the endocrine system, but consumed by eating phytoestrogenic plants. Stem cell enhancer (SCE) (StemEnhance®) is a novel mobilizer of bone marrow adult stem cells that was shown to increase the number of circulating stem cells. Objectives: The aim of the current work was to clarify the effect of both BPA and liquorice together on some sexual hormones and illustration of the effect of stem cell enhancer on their actions. Materials and methods: Thirty male albino rats were used and were divided into three groups: Group I: control (untreated group), group II: rats treated with BPA and liquorice and group III: rats treated with BPA and anise oil in addition to stem cell enhancer. Blood samples were collected for different biochemical investigations. Results: There was a highly significant increase (p < 0.01) in the level of ALT and AST activities, urea, creatinine, FSH, prolactin, total cholesterol, triglycerides, LDL-C, VLDL, LDL/HDL and TC/HDL. While, there was highly significant decrease (p < 0.01) in HDL-C, total protein, albumin, globulin, testosterone and LH. These results turned back to the normal values after receiving the SCE as compared to normal group. Conclusion: It could be concluded that phytoestrogen and xenoeostrogen have undesirable effects and it is recommended to minimize the utilization of these compounds to protect people from its hazardous effects.

Effect of Both Bisphenol - A and Liquorice on Some Sexual Hormones in Male Albino Rats and Illustration of the Effect of Stem Cell Enhancer on Their Actions

Background: Xenoestrogens are a type of xenohormone that imitates estrogen. They can be either synthetic or natural chemical compounds. Synthetic xenoestrogens include some widely used industrial compounds, such as PCBs, bisphenol A (BPA) and phthalates. Dietary estrogen is also called phytoestrogen, which is a plantderived xenoestrogen not generated within the endocrine system, but consumed by eating phytoestrogenic plants. Stem cell enhancer (SCE) (StemEnhance®) is a novel mobilizer of bone marrow adult stem cells that was shown to increase the number of circulating stem cells. Objectives: The aim of the current work was to clarify the effect of both BPA and liquorice together on some sexual hormones and illustration of the effect of stem cell enhancer on their actions. Materials and methods: Thirty male albino rats were used and were divided into three groups: Group I: control (untreated group), group II: rats treated with BPA and liquorice and group III: rats treated with BPA and anise oil in addition to stem cell enhancer. Blood samples were collected for different biochemical investigations. Results: There was a highly significant increase (p < 0.01) in the level of ALT and AST activities, urea, creatinine, FSH, prolactin, total cholesterol, triglycerides, LDL-C, VLDL, LDL/HDL and TC/HDL. While, there was highly significant decrease (p < 0.01) in HDL-C, total protein, albumin, globulin, testosterone and LH. These results turned back to the normal values after receiving the SCE as compared to normal group. Conclusion: It could be concluded that phytoestrogen and xenoeostrogen have undesirable effects and it is recommended to minimize the utilization of these compounds to protect people from its hazardous effects.

The Association between Dietary Patterns and Breast Cancer Pathobiological Factors Progesterone Receptor (PR) and Estrogen Receptors (ER): New Findings from Iranian Case-Control Study

Background: Breast cancer (BrCa) is the most frequently diagnosed cancer among females and second cancer after lung cancer in many societies. Ignoring the phenotypes of the BrCa can affect the interpretation of the association between diet and BrCa. The aim of this study was to determine the association between dietary patterns and estrogen receptor (ER), and progesterone receptor (PR) status in women with BrCa.Methods: This study includes 150 cases of BrCa. Controls were 150 healthy adults, frequency matching based on age. The individual information, food frequency questionnaire, and physical activity were completed while interviews. Information about the pathologic factors obtained from patients' files. Factor analysis method used to determine the dietary patterns; logistic regression used to measure the odds ratios.Results: Getting upper median intake of unhealthy diet had a strong association with BrCa-positive ER and positive PR (OR: 4.98, 95% CI: 2.65–9.34 and OR: 4.99, 95% CI: 2.56–9.75, respectively) compared to under median intake of unhealthy diet. In addition, the protective effect of the healthy diet was stronger on BrCa-negative ER, negative PR (OR: 0.11, 95% CI: 0.04–0.34 and OR: 0.10, 95% CI: 0.03–0.25, respectively).Conclusion: The protective effect of a healthy dietary pattern was stronger on BrCa negative ER and negative PR. The unhealthy dietary pattern had a strong association with BrCa positive ER and positive PR.

Nutritional and Biological Assessment of Some Dietary Estrogen

Nutritional and Biological Assessment of Some Dietary Estrogen

Comparative estrogenicity of endogenous, environmental and dietary estrogens in pregnant women II: Total estrogenicity calculations accounting for competitive protein and receptor binding and potency

Evaluating the biological significance of human-relevant exposures to environmental estrogens involves assessing the individual and total estrogenicity of endogenous and exogenous estrogens found in serum, for example from biomonitoring studies. We developed a method for this assessment by integrating approaches for (i) measuring total hormone concentrations by mass spectrometry (Fleck et al., 2018), (ii) calculating hormone bioavailable concentrations in serum and, (iii) solving multiple equilibria between estrogenic ligands and receptors, and (iv) quantitatively describing key elements of estrogen potency. The approach was applied to endogenous (E1, E2, E3, E4), environmental (BPA), and dietary Genistein (GEN), Daidzein (DDZ) estrogens measured in the serum of thirty pregnant women. Fractional receptor occupancy (FRO) based estrogenicity was dominated by E1, E2 and E3 (ER-α, 94.4–99.2% (median: 97.3%), ER-β, 82.7–97.7% (median: 92.8%), as was the total response (TR), which included ligand specific differences in recruitment of co-activator proteins (RCA). The median FRO for BPA was at least five orders of magnitude lower than E1, E2 and E3, and three orders of magnitude lower than the fetal derived E4 and GEN and DDZ. BPA contributed less than 1/1000th of the normal daily variability in total serum estrogenicity in this cohort of pregnant women.

Comparative estrogenicity of endogenous, environmental and dietary estrogens in pregnant women I: Serum levels, variability and the basis for urinary biomonitoring of serum estrogenicity

Biomonitoring of human exposure to estrogens most frequently focuses on environmental and dietary estrogens, and infrequently includes measures of exposure to potent endogenous estrogens present in serum. Pregnancy is a developmentally sensitive period during which “added” serum estrogenicity exceeding normal intra-individual daily variability may be of particular relevance. We made repeated measurements of serum concentrations of estrone (E1), estradiol (E2), estriol (E3), estetrol (E4), daidzein (DDZ), genistein (GEN) and bisphenol A (BPA) in thirty pregnant women using ultra-performance liquid chromatography coupled with tandem mass spectrometry detection (UPLC-MS/MS) and electrospray ionization (ESI). Serum E1, E2, and E3 concentrations varied significantly (coefficients of variation 9–10%) with broad ranges across the cohort: 1.61–85.1 nM, 9.09–69.7 nM, and 1.5–36.3 nM respectively. BPA (undetected, estimated from total exposure), DDZ and GEN concentrations were 1-5 orders of magnitude lower. The 24-h urinary elimination profiles of endogenous estrogens were each strongly correlated with their corresponding serum concentrations (Pearson's Correlation Coefficients of 0.83 (E1), 0.84 (E2) and 0.94 (E3)). A multivariate regression analysis produced equations for estimating serum concentrations of E1, E2, E3, E4, GEN and DDZ from urinary elimination rates and gestation period, an important step towards non-invasive biomonitoring for assessment of “added” estrogenicity during pregnancy.

Effect of dietary estrogens from bovine milk on blood hormone levels and reproductive organs in mice

Cows are often milked until 60 d before their next expected calving. Milk from cows in the third trimester of pregnancy contains up to 20 times more estrogens than milk from nonpregnant cows. The aim of this study was to evaluate whether exposure to known doses of estrogens from bovine milk could affect blood hormone levels in mice and influence their reproductive organs. This study was performed with 30 intact male and 30 ovariectomized female mice. Mice of each sex were randomly divided into 3 experimental groups, each with 6 animals of each sex, and a control group with 12 animals of each sex. The first experimental group received 4mL of milk each day from a pregnant cow with natural estrone (E1) and 17β-estradiol (E2) in concentrations 0.093 and 0.065ng/mL, respectively. The second experimental group received 4mL of the same milk each day, with an added 10ng/mL of both E1 and E2. The third experimental group received 4mL of the same milk each day, with an added 100ng/mL of both E1 and E2. The control group received no milk. After 8 d of treatment, mice were euthanized, blood was collected, and the uteruses, testes, and seminal vesicles were weighed. The results of our study demonstrated that consumption of native milk from a pregnant cow did not affect plasma E1 and E2 levels in either sex; uterine weight in females; or testosterone levels and testes and seminal vesicle weights in males. Similarly, we found no changes in the group that received the milk with an added 10ng/mL of E1 and E2. We did observe elevated plasma estrogens in both sexes, increased uterus weight in females, and decreased plasma testosterone levels in males from the group that received milk with an added 100ng/mL of E1 and E2. However, concentrations in the third group exceeded the physiological concentration of milk estrogens by 1,000 times, so it would be extremely unlikely to find such concentrations in native cow milk.

Urine and serum biomonitoring of exposure to environmental estrogens II: Soy isoflavones and zearalenone in pregnant women

Urine and serum biomonitoring was used to measure internal exposure to selected dietary estrogens in a cohort of 30 pregnant women. Exposure was measured over a period comprising one-half day in the field (6 h) and one day in a clinic (24 h). Biomonitoring of the dietary phytoestrogens genistein (GEN), daidzein (DDZ) and equol (EQ), as well as the mycoestrogen, zearalenone (ZEN) and its congeners, was conducted using UPLC-MS/MS. Biomonitoring revealed evidence of internal exposure to naturally occurring dietary estrogens during pregnancy. Urinary concentrations of total GEN, DDZ and EQ were similar to levels reported for general adult U.S. population. Measurable concentrations of total (parent and metabolites) GEN, DDZ and EQ were present in 240, 207 and 2 of 270 serum samples, respectively. Six out of 30 subjects had measurable concentrations of unconjugated GEN and/or DDZ in serum between 0.6 and 7.1 nM. Urine to serum total isoflavone ratios for GEN, DDZ and EQ were 13, 47, and 180, respectively. ZEN and its reductive metabolite, α-zearalenol (α-ZEL), were present in pregnant women (11 out of 30 subjects) as conjugates at levels near the limit of quantification. The average total urinary concentration was 0.10 μg/L for ZEN and 0.11 μg/L for α-ZEL.

Roles of Dietary Phytoestrogens on the Regulation of Epithelial-Mesenchymal Transition in Diverse Cancer Metastasis.

Epithelial-mesenchymal transition (EMT) plays a key role in tumor progression. The cells undergoing EMT upregulate the expression of cell motility-related proteins and show enhanced migration and invasion. The hallmarks of EMT in cancer cells include changed cell morphology and increased metastatic capabilities in cell migration and invasion. Therefore, prevention of EMT is an important tool for the inhibition of tumor metastasis. A novel preventive therapy is needed, such as treatment of natural dietary substances that are nontoxic to normal human cells, but effective in inhibiting cancer cells. Phytoestrogens, such as genistein, resveratrol, kaempferol and 3,3′-diindolylmethane (DIM), can be raised as possible candidates. They are plant-derived dietary estrogens, which are found in tea, vegetables and fruits, and are known to have various biological efficacies, including chemopreventive activity against cancers. Specifically, these phytoestrogens may induce not only anti-proliferation, apoptosis and cell cycle arrest, but also anti-metastasis by inhibiting the EMT process in various cancer cells. There have been several signaling pathways found to be associated with the induction of the EMT process in cancer cells. Phytoestrogens were demonstrated to have chemopreventive effects on cancer metastasis by inhibiting EMT-associated pathways, such as Notch-1 and TGF-beta signaling. As a result, phytoestrogens can inhibit or reverse the EMT process by upregulating the expression of epithelial phenotypes, including E-cadherin, and downregulating the expression of mesenchymal phenotypes, including N-cadherin, Snail, Slug, and vimentin. In this review, we focused on the important roles of phytoestrogens in inhibiting EMT in many types of cancer and suggested phytoestrogens as prominent alternative compounds to chemotherapy.

천연물로부터 여성갱년기 증상완화를 위한 식물성 에스트로겐의 초음파 추출특성

Phytoestrogens are plant-derived xenoestrogens not generated within the endocrine system but consumed by eating phytoestrogenic plants. Also called “dietary estrogens”, they are a diverse group of naturally occurring nonsteroidal plant compounds that, because of their structural similarity with estradiol (17-β-estradiol), have the ability to cause estrogenic or/and antiestrogenic effects. Phytoestrogen may provide desirable health benefits to reduce the menopausal symptoms. There are various types of phytoestrogens. In an experiment, various estrogens were extracted from kudzu, sophora root and pomegranate by using a ultrasonic extraction process in a various conditions. The results obtained from this will serve as basic data in the study of biology and chemistry related to natural products.

Dietary estrogens and working memory in a perimenopausal rodent models

Dietary estrogens and working memory in a perimenopausal rodent models

Abstract A22: Associations between dietary intake and novel genotoxic estrogen biomarkers implicated in breast cancer risk

Abstract Background: An expansive body of evidence implicates estrogen in the development of breast cancer (BC). Recently, a novel estrogen biomarker, the genotoxoic estrogen ratio (GER), was shown to be associated with BC. In addition, an elevated GER was observed in women at high-risk of BC, and furthermore, high GER has been shown to be reversible. Because of the potential for phytochemicals to inhibit activating enzymes and induce protective enzymes within the metabolism pathway resulting in reduced GER, we sought to examine associations between dietary factors and GER. Methods: This analysis was conducted in 53 pre-menopausal, healthy women aged 40-45 years from a cross-sectional study in which participants provided first-void urine samples and 3-day food records. The estrogen metabolites, conjugates and depurinating DNA adducts comprising the GER were identified from urine samples using ultraperformance liquid chromatography/ tandem mass spectrometry. The numerator of GER contains estrogen compounds which are bound to DNA as depurinating adducts, and thus have the potential to be genotoxic; the denominator contains the unbound estrogen counterparts consisting of estrogen metabolites and conjugates. A trend test was used to assess associations between tertiles of nutrient and food intake. Results: We observed GER to be associated with dietary intake after adjustment for age, total calories, percent adiposity, and estradiol. Specifically, elevated GER was associated with low vegetable intake (p=0.01), low carbohydrate consumption (p=0.01), low botanical intake (p=0.04), and high animal protein consumption (p=0.05). In particular, elevated GER was associated with the increasing servings of eggs (p=0.01) and fish (p=0.02) per day. In addition, low GER was associated with three botanical groupings: highest category of umbelliferae consumption (which includes carrots and celery; p=0.01), middle category of cruciferae consumption (which includes broccoli and cabbages; p=0.05), and middle category of ericaceae consumption (which includes blueberries and cranberries; p=0.05). Conclusion: These data provide the first investigation of lifestyle factors in relation to this novel GER biomarker. While these data would require replication, this early report suggesting inverse associations between dietary intake of botanical foods and GER provides an intriguing link between dietary factors and a novel biomarker with implications for breast cancer risk. Citation Format: Kerryn W. Reding, Muhammed Zahid, Ercole Cavalieri, Eleanor G. Rogan, Charlotte Atkinson, Mellissa Yong, Katherine Newton, Johanna Lampe. Associations between dietary intake and novel genotoxic estrogen biomarkers implicated in breast cancer risk. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A22.

A comparative study between the effects of dietary soya and estrogen replacement therapy on the lung of ovariectomized albino rats

A comparative study between the effects of dietary soya and estrogen replacement therapy on the lung of ovariectomized albino rats

Regulation of adiponectin secretion by soy isoflavones has implication for endocrine function of the testis

Testicular Leydig cells are the predominant source of the male sex steroid hormone testosterone (T), which is required to maintain male fertility. There is now growing evidence that environmental stressors, including chemicals present in food, air and water, may affect energy balance. A relationship between energy balance and reproductive capacity has been proposed for a long time. In the present study, developmental exposures of male rats to soy isoflavones in the maternal diet from gestational day 12 to day 21 post-partum enhanced adiponectin expression in adipose tissue and increased serum adiponectin concentrations in adulthood. However, exposure to soy isoflavones caused a decrease in T production and expression of adiponectin and its receptor (adipoR2) in Leydig cells. In separate experiments, incubation of Leydig cells with recombinant adiponectin in the absence of isoflavones caused a decrease in T biosynthesis associated with diminished expression of the cholesterol transporter steroidogenic acute regulatory protein (StAR). Thus, chemical-induced alterations in serum adiponectin concentrations have implication for steroid hormone secretion. The results also imply that changes in adipose tissue metabolism occasioned by exposure to dietary estrogens, and perhaps other estrogenic agents, possibly contribute to deficiencies in reproductive capacity attributed to these compounds.

Proliferative effect of whey from cows' milk obtained at two different stages of pregnancy measured in MCF-7 cells

Dietary estrogens may play a role in the etiology of hormone-dependent cancers like breast cancer. Cow's milk contains various endogenous estrogens and feed derived phytoestrogens that potentially contribute to an estrogenic effect of milk in consumers, and therefore we evaluated the effect of milk (whey) in a proliferation assay with estrogen-sensitive MCF-7 human breast cancer cells. Milk samples were obtained from 22 cows representing different stages of pregnancy (first and second half) and whey was produced from the milk. 0·1, 0·25 or 0·5% whey was included in the cell culture medium and after 6 days of treatment cell proliferation was assessed by a colorimetric method with a fluorometer. Whey induced significant (P<0·05) proliferative effects compared with control cells with no added whey at all concentrations tested. There was no difference in the proliferative effect of whey depending on the stage of pregnancy from which the milk was obtained. We did not observe anti-proliferative effects when whey was tested in the presence of 10 pm estradiol in the medium. In conclusion, these results indicate that whey, irrespective of the pregnancy stage from which the milk was obtained induced a significant proliferative response in MCF-7 cells and no anti-proliferative effect, which may be caused, at least in part, by estrogens present in milk. The implications of our findings in relation to for example breast cancer will have to be studied further in other model systems preferentially in vivo.

In this issue

AbstractAssociations meet on a rarely traveled/trampled road: Corner of Yellow Brick Road and Appian WayNo room number or hotel specified. Ising required. This is not cake frosting in a can. So, what is the Ising model? Originally, a mathematical model devised to study magnetic fields, it was soon recognized as a powerful model for studies of inheritance. Unlike on/off models of genes, Ising genes are two‐state: +1 or −1 and describe the spin states of a magnetic dipole or the state of an allele that might or might not be shared by siblings. I'll save you the 14 equations that Li et al. apply to the model – they are not impenetrable. Working with an Affymetrix data set, 286 patients were lymph node negative to start. A Markov Random Field model identified 107 Differentially Expressed (DE) genes and the Ising model found 125. These included a number of previously unknown and unclassified networks and subnetworks.pp. 3845–3852Taxol, you've been a wonderful drugBut you've let me down, lately. Breast cancer is still the no. 1 killer of women. Prognosis is poor due to late tumor detection or rapid drug resistance. Some multiple drug combinations fail too frequently but Taxanes in combination with anthracyclines or Herceptin give some improvement, depending on the genetics of the patient (“personalized medicine”). The mechanism of action of the taxane resistance involves interactions with microtubules including β‐tubulin mutations, insufficient cyclin‐dependent kinase I, modulation of ERB‐B2, p53, or Bcl‐2. On the other hand, protein kinase phosphatase MKP‐1 has been nominated to mediate chemoresistance by inhibiting c‐Jun N kinase‐dependent apoptosis. Choices, choices, choices....pp. 3877–3886His and hers: Cardiovascular eventsSex‐change operations do not help: cardiovascular disease is the leading cause of morbidity and mortality among both men and women if you adjust for age and menopause, inferring that both androgens and estrogens are contributors to the disease. Estrogen replacement has proven to have some protective value but results appear to be conflicting in human trials. Phytoestrogens are a group of potential candidates derived from plant materials. A particularly interesting compound is genistein (as long as the experimenter controls for variable levels in common lab chow). Schwab et al. took environmental age, sex, and heart condition into consideration in the proteomic study reported here. Addition of genistein as an oral dietary estrogen supplement had effects on both male and female mice at the levels of transcription and translation. Mitochondrial enzymes were affected, including fatty‐acid metabolism, oxidative phosphorylation, and cytoskeletal components. Clearly obscure...pp. 3887–3904