Differences In Estrogen Levels Research Articles

Metagenomic characterization of the equine endometrial microbiome during anestrus

Recent studies have confirmed that healthy uteri, including the equine uterus, harbour a microbiome. Studies on mares have been performed in estrus and therefore under the influence of high estrogen concentrations. Multiple human studies investigating the vaginal, as well as the gut microbiome have shown that the microbiome is dynamic throughout the estrous cycle and is influenced by differences in estrogen levels. This is in contrast to a study performed on Arabian mares which indicated that the equine vaginal microbiome is stable throughout the estrous cycle.In this study the resident uterine microbiome of healthy anestrous mares was characterized by metagenomics from double-guarded endometrial swabs and compared to the microbiome in the same mares during estrus.Double guarded endometrial swabs from 15 healthy estrous mares were taken and stored at -80°C until extraction, in the following non-breeding season 8 mares from this group were sampled in similar fashion during anestrus. Blank samples were obtained during both sample period. Genomic DNA was extracted using Qiagen DNeasy PowerSoil extraction kits and 16S rRNA gene was amplified using primers 515f-806r. An amplicon sequence variant table was made and chimeras were removed and the genomic16S rRNA from the blank samples was substracted. Sequences were processed and analysed using 16S rRNA SILVA v138.1 database. Contaminating reads were removed from the samples by subtracting the reads from the blank samples using Microdecon and downstream analysis performed using the Phyloseq package. Alpha and beta diversity were calculated using microbiome, amplicon and vegan packages.Results suggest that the equine uterine microbiome in estrus has a low diversity, low richness, and a low abundance at phylum level. The equine uterine microbiome in anestrus has a higher diversity, higher richness, and higher abundance compared to the estrus uterine microbiome. However, both the estrus as well as the anestrus endometrial microbiome is dominated by Proteobacteria, Firmicutes, and Bacteroidota. PCoA analysis displays a strong dissimilarity between estrus and anestrus samples.The difference in the microbiome between estrus and anestrus can possibly be explained due to the variance in immune responsiveness of the endometrium. The estrous mare's endometrium is under the influence of estrogens, allowing for a high immune response and possibly less diverse microbiome.

The impact of pre-treatment plasma sex hormones on the immune checkpoint inhibitors response to metastatic non-small cell lung cancer.

e21088 Background: Immune checkpoint inhibitors (ICI) have changed the outcomes in metastatic non-small cell lung cancer (mNSCLC). The immune system partially determines the response to ICI. The impact of sex hormones on immune responses is well recognized in autoimmune disease and vaccine response. Little is known about the interplay between the sex hormones and the response to ICI in mNSCLC. Methods: This prospective, observational study included patients with mNSCLC at Moffitt Cancer Center who received ICI as monotherapy or combination with chemotherapy. Plasma was collected before the first ICI infusion. Extraction and detection of the hormones were optimized by modifying the previous method. Hormone levels were measured using ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS). Estrogens included propyl pyrazole triol (PPT), 17β-estradiol (E2), and S-equol. Androgens included 5-androstenediol, 3β-androstenediol (3β-diol), and dehydroepiandrosterone (DHEA).Patients were divided based on clinical benefits, defined as a complete or partial response or stable disease for at least 12 months. Categorical variables were compared using the Chi-square test or Fischer exact test; continuous variables were compared using the Mann-Whitney U test. Results: Sixty-one patients were included and 50.8% were female. The median age was 67 years. Twenty-eight patients had clinical benefits from ICI. Patients in the clinical benefit group had higher BMI. The clinical benefit group had significantly lower androgen levels but no difference in estrogen levels. The median DHEA level was 3.7 ng/ml in the clinical benefit group and 9.6 ng/ml in the group without (p < 0.001). The 5-Androstenediol was also lower in the clinical benefits group (table I). When normalized to the age/sex-adjusted reference range, the difference of DHEA and 5-androstenediol was retained (p < 0.001 and 0.014, respectively). 3β-diol was below the limit of detection. Conclusions: The serum DHEA and 5-androstenediol levels were lower in mNSCLC patients who benefited from ICI, regardless of sex. Larger studies are needed to confirm the role of pre-treatment androgens levels as negative biomarkers for ICI response. [Table: see text]

Cancer Progress and Priorities: Breast Cancer.

Breast cancer is the most commonly diagnosed invasive cancer among women both globally and within the United States and the number one cause of cancer-related deaths among women globally ([1, 2][1]). Less than 1% of diagnosed breast cancers occur in men ([2][2]) and, therefore, male breast cancer is

The administration of UltraMimi Kids® UHT milk by PT. Ultrajaya Milk Industry increased body weight and did not increase estrogen hormone level in female albino rat (Rattus norvegicus) Wistar strain

Background: This study aimed to prove that administration of UltraMimi Kids® UHT milk by PT. Ultrajaya Milk Industry increased body weight and estrogen levels in female albino rat (Rattus norvegicus) Wistar strain.
 Methods: This research was a true experimental with randomized pretest-posttest control group design. The research subjects were 18-female-albino-rats aged 21-days, weight 25-28 grams, divided into 2-groups: control group which was given standard food and sugar solution (0.36 grams of sugar dissolved in 1 ml aquadest), and intervention group which was given standard food and UltraMimi Kids® UHT milk 1 ml for the first 14-days and upgraded to 2 ml for the rest 14-days, given three times a day for 28-days. The rats body weight and estrogen levels were measured using Tanita-KD-192-digital-scales and ELISA method.
 Results: The control group had an increased body weight (26.2±1.2-66.1±5.94 grams; p<0,001), but there was no change in estrogen levels (38.59±11.19-44.59±5.42 ng/L; p=0.217). Whereas, the intervention group had an increased body weight (25.77±0.83-85.33±10.24 grams; p=0.008), but there was no change in estrogen levels (39.91±3.73-42.66±2.24 ng/L; p=0.066). After 28-days of intervention (posttest), it was found that the mean of body weight in the intervention group was higher than the control group (p<0.001), there was no significant difference in estrogen levels (p=0.339) and food intake from the remaining feed in both groups (0.51±0.81-0.36±0.55 grams; p=0.823).
 Conclusion: The administration of UltraMimi Kids® UHT milk by PT. Ultrajaya Milk Industry increased body weight and did not increase estrogen hormone level in female albino rat (Rattus norvegicus) Wistar strain.

A Comparative Study of Vitamin D Levels and Some Biochemical Parameters between Healthy and Breast Cancer in Iraqi Females

Breast cancer is one of the most widespread cancers,depending on World Health Organization, cancer calculated for approximately 7.6 million incidences in 2008, whoever expected elevation in incidence is about 13.1 million in 2030. So that the current research investigates vitamin D role in the occurrence of this disease and explains if vitamin D has a positive effect on the incidence of disease, as well as measuring parathyroid hormone and estrogen levels. Three groups were included in this analysis: control healthy women, benign and malignant breast tumor women. All cases that were selected at the beginning of the disease diagnosis. According to statistical values vitamin D showed highly significant (P<0.001) decrease in benign (3.74±2.33) ng/ml and malignant (4.38±3.12) ng/ml tumor patients compared with healthy group (24.96±7.24) ng/ml. Also a high significant increase was shown for PTH values in benign (208.37±132.5) pg/ml and malignant (133.9±60.02)pg/ml tumor patients compared with healthy group (67.04±25.6) pg/ ml. Furthermore, results revealed non-significant difference in estrogen levels between benign group (54.11±22.93) pg/ml, and control group (64.85±22.18)pg/ml, while there were a significant difference in levels of estrogen between control and malignant tumor groups (52.4±18. 09) pg/ml. As a results, we found that all patients had sever vitamin D deficiency compared with healthy group, as well as high levels of parathyroid hormone as evidence of vitamin D deficiency, while estrogen levels where within normal levels. We concluded that all patient groups were suffering from vitamin D deficiency and elevation in parathyroid hormone that gives evidence of the role of vitamin D as anti-cancer agent.

Effects of oral contraceptive use on female sexual salivary hormones and indirect markers of muscle damage following eccentric cycling in women.

To determine the effects of oral contraceptive (OC) use on salivary concentrations of testosterone, estrogen, progesterone, and its effects on the changes in indirect markers of muscle damage following eccentric cycling in women. 10 oral contraceptive users at follicular phase (OC-FOL), 10 non-oral contraceptives users at follicular phase (NOC-FOL), and 10 non-oral contraceptives users at ovulation phase (NOC-OV) participated. Subjects performed 30min of eccentric cycling at 90% of their maximal concentric power output (PO). Maximal voluntary isometric contraction (MVC), creatine kinase activity (CK), muscle soreness (SOR), and pain pressure threshold of vastus lateralis (PPT-VL) was assessed before, immediately after, and 24-96h after cycling. Salivary estrogen, progesterone and testosterone concentrations were measured before, 72 and 96h after exercise. No difference in estrogen levels between users and non-users was observed. Testosterone was 45% lower in OC-FOL than NOC-FOL at 96h post-exercise (P = 0.01). Progesterone was 30.8-fold higher in NOC-OV than OC-FOL and 9.7-fold higher than NOC-FOL at 96h post-exercise. The NOC-FOL recovered all indirect markers of muscle damage by 72h post-exercise (P > 0.05). NOC-OV recovered MVC strength and muscle soreness (SOR and PPT-VL) by 96h post-exercise (P > 0.05). OC-FOL did not recover baseline values of MVC, SOR, CK, and PPT-VL by 96h. These results suggest that recovery after exercise-induced muscle damage took longer in OC-FOL, followed by NOC-OV and by NOC-FOL, respectively. Furthermore, testosterone and progesterone levels may affect recovery of indirect markers of muscle damage in women.

Combination therapy with BMP-2 and psoralen enhances fracture healing in ovariectomized mice.

The advantages of combining local delivery of bone morphogenetic protein (BMP)-2 with systemic or local anti-osteoporosis treatments have also been studied for enhancing osteoporotic fracture healing. The aim of the present study was to evaluate the effect of combination therapy with BMP-2 and psoralen on fracture repair in ovariectomized mice. At 6 weeks after bilateral ovariectomy, mice (n=30) underwent unilateral transverse osteotomy on the femur and were divided into 3 groups. In the model group (n=10), animals were implanted with an absorbable collagen sponge (ACS) alone and administered physiological saline intragastrically (i.g.). In the recombinant human (rh)BMP-2 group (n=10), animals were implanted with an ACS loaded with 2.5 µg rhBMP-2 and administered physiological saline i.g. In the psoralen + rhBMP-2 group (n=10) animals were implanted with an ACS loaded with 2.5 µg rhBMP-2 and administered psoralen i.g. The mice were euthanized after 21 days and their fractured femurs were assessed by micro computed tomography, histological analysis and biomechanical testing. Furthermore, the serum of the animals was analyzed. Psoralen + rhBMP-2 exerted more beneficial effects on callus consolidation and biomechanical strength. In addition, increased bone-specific alkaline phosphatase levels and decreased C-terminal telopeptide of type-1 collagen were observed in the Psoralen + rhBMP-2 group. However, no difference in estrogen levels was detected between the groups. In conclusion, the present study demonstrated that in ovariectomized mice, combination of locally delivered BMP-2 and systemically administered psoralen improved bone healing compared with BMP-2 alone.

Effectiveness of Fish Oil Supplementation in Attenuating Exercise-Induced Muscle Damage in Women During Midfollicular and Midluteal Menstrual Phases.

McKinley-Barnard, SK, Andre, TL, Gann, JJ, Hwang, PS, and Willoughby, DS. Effectiveness of fish oil supplementation in attenuating exercise-induced muscle damage in females during midfollicular and midluteal menstrual phases. J Strength Cond Res 32(6): 1601-1612, 2018-The purpose of this study was to determine whether the differences in estrogen levels during the female menstrual cycle and fish oil supplementation would attenuate eccentric exercise-induced muscle damage and delayed-onset muscle soreness (DOMS). In a double-blind fashion, 22 physically active females (20.9 ± 1.4 years, 63.5 ± 9.0 kg, 165.2 ± 7.5 cm) were randomly assigned to ingest either 6 g of fish oil (n = 11) or placebo (n = 11) daily for 21 days. Participants underwent an eccentric exercise bout of the knee extensors on 2 occasions during the midfollicular (MF) and midluteal (ML) phases of the 28-day menstrual cycle. Before (PRE), at 6 (6HRPOST), and at 24 hours postexercise (24HRPOST) for each session, participants underwent assessments of DOMS, muscle strength, and had venous blood samples and muscle biopsies obtained. Data were analyzed using a 2 × 2 × 3 repeated-measures multivariate analysis of variance for each criterion variable (p ≤ 0.05). Further analysis of the main effects for the test was performed using separate 1-way analyses of variance. Delayed-onset muscle soreness was significantly greater at the 6HRPOST and 24HRPOST timepoints compared with PRE (p < 0.001). Superoxide dismutase and tumor necrosis factor-alpha (TNF-α) concentrations were significantly higher at the MF phase compared with the ML phase (p < 0.001 and p = 0.05, respectively). There were no statistically significant differences observed for muscle strength, myoglobin, NF-Kβ p50, or NF-Kβ p65. This study demonstrates that higher levels of estrogen may exert a cytoprotective effect on the sarcolemma.

Lifetime endogenous estrogen exposure and disease severity in female patients with facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by large variability in disease severity, that is only partly explained by (epi)genetic factors. Clinical observations and recent in vitro work suggest a protective effect of estrogens in FSHD. The aims of this study were to assess whether the lifetime endogenous estrogen exposure contributes to the variability in disease severity in female patients, and whether female patients experience changes in disease progression during periods of hormonal changes. We calculated the lifetime endogenous estrogen exposure by subtracting periods with high progesterone levels (in which estrogens are counteracted) from the reproductive life span. Multiple linear regression in 85 patients did not show a contribution of the lifetime endogenous estrogen exposure to disease severity (B = 0.063, P-value = 0.517, ΔR2 = 0.003). The majority of women reported an unchanged rate of disease progression through periods of hormonal changes, like menarche, pregnancy or menopause. Women that noticed differences reported accelerations as well as decelerations. These results indicate that differences in estrogen exposure do not have a clinically relevant modifying effect on disease severity. However, a clinically relevant protective effect of greater differences in estrogen levels, or a protective effect caused by a more complex interplay with other reproductive hormones, cannot be ruled out.

Relationship Between Polymorphism in Exon 8 of Estrogen Receptor Alpha Gene and Osteoporosis in Saudi Women

Objectives: Alternations in the estrogen receptor alpha gene (ERα) play an essential role in osteoporosis etiology. In this study, the relationship between a single nucleotide polymorphism (SNP) in ERα (G2014A) and osteoporosis in Saudi women were investigated. Methods: In this research 40 females with osteoporosis and 41 healthy controls ranging in age from 35 to 75 years were examined. Demographic data were recorded, and blood samples were drawn in plain and in EDTA tubes for estimation of estrogens in the serum and extraction of DNA, respectively. The DNA was used to amplify the fragment of interest carrying the SNP in ERα by polymerase chain reaction (PCR). The PCR product was subjected to DNA sequencing. Results: G2014A was polymorphic in Saudi women. Genotypes and allele frequencies were compared in the osteoporotic and non-osteoporotic groups. Although the genotypes of osteoporotic and non-osteoporotic subjects were significantly different (p=0.0157), the allelic frequency was not significantly different (p=0.519). Estrogen levels significantly differed between osteoporotic and nonosteoporotic subjects (mean ± SD E2: 46.6 ± 30.7 vs. 68.7 ± 47.1 pg/mL, p=0.0143). Importantly, a significant difference in waist-hip ratio in osteoporotic patient and the nonosteoporotic group was detected (0.8 ± 0.1 vs. 0.9 ± 0.0, p=0.0174). Conclusion: Although there was no relationship between G2014A and osteoporosis in Saudi women, this study sheds light on another aspect, such as the significant difference in estrogen levels in these two groups. Furthermore, an advantageous effect of fat on bone mass was observed in the non-osteoporotic group.

Changes of sex hormone level in perinatal depression in different perinatal periods

Objective To study the correlation between the changes of sex hormone level in different perinatal periods and perinatal depression (PND). Methods Between February 2014 and February 2015, 300 pregnant women from the Third Affiliated Hospital of Guangzhou Medical University were enrolled in this study. In the first trimester (12 weeks), the third trimester (34 weeks) and postpartum period (7 and 42 days), blood samples were collected and radioimmunoassay was performed to detect the levels of sex hormones, including estrogen, progesterone, prolactin, luteinizing hormone and follicle-stimulating hormone. Self Depression Scale and Edinburgh Postnatal Depression Scale were used for psychological assessment, and PND was diagnosed by psychiatrists as PND group, and non-PND cases served as control group. Two-sample t-test, variance analysis and Bonferroni test were used to compare the changes of sex hormones at different time points between the two groups. Results A total of 180 pregnant women completed the four stages of research. Fifity-four cases were diagnosed as PND, including 10 cases in the first trimester, 16 new cases in the third trimester, 14 new cases at postpartum 7 days, and 14 new cases at postpartum 42 days. (1) Comparison of the sex hormone levels between the two groups: The estrogen levels of the first trimester, the third trimester and postpartum 7 and 42 days in PND group were (4 107.30±344.68), (13 261.60±593.32), (1 281.70±151.54) and (161.40±12.21) pmol/L, and lower than in the control group [(8 619.60±514.92), (14 330.00±353.15), (3 585.90±150.83) and (270.50±11.86) pmol/L, respectively] (all P<0.05). The progesterone levels of the first trimester and postpartum 7 and 42 days in PND group were (105.49±20.40), (24.23±3.53) and (6.40±3.53) nmol/L, and higher than those in the control group [(85.80±19.06), (5.71±2.36) and (3.87±2.03) nmol/L] (t=-2.389, -2.660 and -2.103, all P<0.05). The prolactin and luteinizing hormone levels of the postpartum 42 days in PND group were lower than in the control group [(9.40±1.69) vs (17.50±1.64) μg/L, t=-4.059; (0.32±0.21) vs (2.21±0.17) mU/L, t=-12.302] (both P<0.05). The levels of follicle-stimulating hormone in the first trimester, the third trimester and postpartum 7 days were not detectable in both groups, but PND group had a lower level at postpartum 42 days than the control group [(2.22±0.58) vs (3.15±0.29) mU/L, t=-15.525, P=0.000]. (2) Sex hormone levels at different time points: There were significant differences in estrogen levels between the four time points in both groups. There was significant difference in progesterone in the PND group at four time points, while in the control group, significant differences were found between postpartum 42 days and the first and third trimester. Prolactin levels were lowest at postpartum 42 days in both groups among the four time points (Bonferroni test, all P<0.05). Conclusions Low estrogen levels and high progesterone levels and their changes in perinatal period may be correlated with PND. Key words: Peripartum period; Depression; Estrogens; Progesterone; Gonadal steroid hormones

Sex, Steroids, and Fear

Psychiatric illness is not an “equal opportunity” disease. For example, the lifetime prevalence of posttraumatic stress disorder (PTSD) is twice as high in women than in men. In recent years, gonadal steroids have moved into the spotlight as a potential key to understanding this sex difference in vulnerability to trauma-related and stress-related disorders (1,2). Many preclinical and clinical studies have implicated ovarian hormones, including estrogen and progesterone, in the modulation of fear and anxiety in women (2). In particular, these hormones play an important role in fear extinction, a form of learning thought to underlie therapeutic interventions that reduce fear in patients with PTSD (1). Ovarian steroids and their metabolites are targets for the development of novel therapeutics for stressrelated disorders (ClinicalTrials.gov Identifier: NCT01339689). As discussed by Glover et al. (1), ovarian hormones play an important role in modulating fear extinction, a form of learning involved in the suppression of learned fear responses. For example, extinction of contextual and auditory fear conditioning is facilitated by estrogen in rodents and humans (2,3). Women in the luteal phase (high circulating estrogen) of the menstrual cycle have stronger extinction recall compared with women in the early follicular phase or on oral contraceptives (low circulating estrogen) (2). In addition to estrogen, progesterone and its neuroactive metabolite, allopregnanolone, have been shown to modulate anxiety and fear. Progesterone treatment in intact female rats facilitates extinction recall (2). A synthetic analogue of allopregnanolone, ganaxolone, has also been shown to facilitate extinction in mice (4). Although progesterone in women has not been linked to enhanced extinction recall (2), it has been implicated in various psychiatric disorders, including major depressive disorder and premenstrual dysphoric disorder (5). The fact that estrogen and progesterone can regulate extinction learning is of particular relevance to PTSD, insofar as patients with PTSD exhibit exaggerated conditioned fear responses (6). Yet there is an enigma: Sex differences in vulnerability to PTSD do not directly correspond to sex differences in estrogen levels. Low estrogen is correlated with deficits in extinction in women but not in men (2). Glover et al. suggest that the key is not absolute levels of estrogen, but rather fluctuations in estrogen levels, that give rise to sex-specific susceptibility. The regulation of fear conditioning and extinction by ovarian steroids in women may account for sex differences in these forms of learning (Figure 1). For example, female rodents exhibit lower levels of conditioned fear and more rapid fear extinction than male rodents, and this effect is mitigated by ovariectomy and restored by estrogen administration (3). However, at least in rodents, sex differences in fear conditioning and extinction are limited to shock-paired contexts. Discrete conditioned stimuli or “cues” support similar levels of fear in male and female rats (2,7,8) and in humans (2), although high estrogen states during extinction training result in weaker extinction recall (Figure 1). A critical gap in the

Estrogen causes ultrastructural changes of fibrin networks during the menstrual cycle: A qualitative investigation

Hormonal fluctuations may influence fibrin structure. During the menstrual cycle, plasma fibrinogen levels change, mainly due to the variations of estrogen. Throughout the menstrual cycle estrogen levels peak twice, first during the mid-follicular phase and then a lower second peak during the luteal phase. In order to investigate the possible changes in the fibrin network throughout the menstrual cycle, the fibrin network ultrastructure of six healthy female participants were studied at different intervals in the menstrual cycle where differences in estrogen levels are prevalent. Blood plasma smears were prepared for scanning and transmission electron microscopy analysis. The external and internal structure of the fibrin fibers showed different morphologies throughout the menstrual cycle. The fibrin fibers were smooth during days 1-5. However, during days 12-14 of the menstrual cycle the fibrin fiber morphology started to change, becoming less smooth. During the luteal phase of the cycle (days 20-25), the network appears sticky, where the minor, thin fibers are more prominent between the thick fibers when compared to the menstrual phase. The two estrogen peaks of the menstrual cycle coincide with the changes seen in the current qualitative research, where the fibrin morphology changes during the same time as the estrogen peaks occur. Purified fibrinogen confirmed that it is indeed estrogen that causes the altered fibrin network morphology. This research is the first to show ultrastructural changes in fibrin fiber morphology resulting from estrogen changes during the menstrual cycle.

The primate vaginal microbiome: Comparative context and implications for human health and disease

The primate body hosts trillions of microbes. Interactions between primate hosts and these microbes profoundly affect primate physiology, reproduction, health, survival, and ultimately, evolution. It is increasingly clear that primate health cannot be understood fully without knowledge of host-microbial interactions. Our goals here are to review what is known about microbiomes of the female reproductive tract and to explore several factors that influence variation within individuals, as well as within and between primate species. Much of our knowledge of microbial variation derives from studies of humans, and from microbes located in nonreproductive regions (e.g., the gut). We review work suggesting that the vaginal microbiota affects female health, fecundity, and pregnancy outcomes, demonstrating the selective potential for these agents. We explore the factors that correlate with microbial variation within species. Initial colonization by microbes depends on the manner of birth; most microbial variation is structured by estrogen levels that change with age (i.e., at puberty and menopause) and through the menstrual cycle. Microbial communities vary by location within the vagina and can depend on the sampling methods used (e.g., swab, lavage, or pap smear). Interindividual differences also exist, and while this variation is not completely understood, evidence points more to differences in estrogen levels, rather than differences in external physical environment. When comparing across species, reproductive-age humans show distinct microbial communities, generally dominated by Lactobacillus, unlike other primates. We develop evolutionary hypotheses to explain the marked differences in microbial communities. While much remains to be done to test these hypotheses, we argue that the ample variation in primate mating and reproductive behavior offers excellent opportunities to evaluate host-microbe coevolution and adaptation.

Getting to the Heart of the Matter: Age-related Changes in Diastolic Heart Function in the Longest-lived Rodent, the Naked Mole Rat

The naked mole rat is an extremely long-lived (>31 years) small (35 g) rodent. Moreover, it maintains good health for most of its long life. We hypothesized that naked mole rats also show attenuated cardiac aging. With age, cardiac muscle can become less compliant, causing a decline in early diastolic filling (E) and a compensatory increase in atrial contraction-induced late filling (A). This results in decreased left ventricular E/A ratio. Doppler imaging showed no significant differences in E/A ratios (p = .48) among old (18-20 years) breeders and nonbreeders despite differences in estrogen levels. A cross-sectional study of 1- to 20-year-old naked mole rats (n = 76) revealed that E/A ratios declined with age in females (n = 40; p = .002) but not in males (n = 36; p = 0.45). Despite this, neither gender shows increased morbidity or mortality with age. These findings suggest that, notwithstanding the previously observed high lipid peroxidation in heart tissue, NMRs must possess mechanisms to stave off progression to fatal cardiac disease.

Association of CYP19A1 polymorphisms with risks for atypical adenomatous hyperplasia and bronchioloalveolar carcinoma in the lungs

Estrogen has been indicated to play an etiological role in the development of lung adenocarcinoma (ADC), particularly bronchioloalveolar carcinoma (BAC), a type of ADC that develops from a benign adenomatous lesion, atypical adenomatous hyperplasia (AAH). Polymorphisms in the CYP19A1 gene cause interindividual differences in estrogen levels. Here, 13 CYP19A1 single-nucleotide polymorphisms (SNPs) were examined for associations with lung AAH risk. AAH is detected as ground-glass opacity (GGO) by computed tomography (CT) examination, and this study consisted of 100 individuals diagnosed with GGO in their lungs among 3088 CT-based cancer screening examinees and 424 without. Minor allele carriers for the rs3764221 SNP showed an elevated risk for GGO [odds ratio (OR) = 1.72, P = 0.017]. Associations of this SNP with risks for lung AAH and BAC in the lungs were next examined using 359 ADC cases whose resected lung lobes were subjected to a histological examination for AAH accompaniment and the presence of BAC components and 330 controls without cancer. The ORs were also increased for lung ADC accompanied by AAH (OR = 1.74, P = 0.029) as well as lung ADC with BAC components (OR = 1.41, P = 0.091). The minor allele was associated with an increased circulating estradiol level (P = 0.079) in a population of 363 postmenopausal women without cancer. These results indicate that CYP19A1 polymorphisms are involved in the risk for lung AAH and BAC in the lungs by causing differences in estrogen levels.

Human Data on Bisphenol A and Neurodevelopment

Human Data on Bisphenol A and Neurodevelopment

Estrogen Promotes Sympathetic Nerve Regeneration in Rat Proximal Urethra

To assess whether sympathetic reinnervation of the rat proximal urethra is affected by differences in estrogen levels. Sympathetic innervation mediates tonic contraction of proximal urethral smooth muscle, thus contributing to urinary continence. Urethral innervation is particularly susceptible to damage during vaginal delivery, a time characterized by decreasing estrogen levels. Adult female rats were ovariectomized and implanted with pellets containing vehicle or estrogen to achieve serum levels similar to rodent pregnancy. The rats were injected intravenously with vehicle or the selective sympathetic neurotoxin 6-hydroxydopamine, which produces uniform and complete destruction of terminal sympathetic axons. At 1, 4, 12, and 25 days, tyrosine hydroxylase-immunoreactive sympathetic innervation of the proximal urethral smooth muscle was assessed quantitatively. In rats with intact innervation, the proximal urethra is densely innervated, and nerve density is comparable, irrespective of estrogen status. 6-Hydroxydopamine induced marked sympathetic axon disruption by day 1 and complete denervation by 4 days after injection in the ovariectomized rats receiving vehicle or estrogen. In the vehicle-treated rats, few nerves were present at 12 days after sympathectomy, and innervation remained substantially less than normal levels at 25 days. In estrogen-treated rats, sympathetic reinnervation was twofold greater at 12 days and by 25 days was comparable to that of the controls. Estrogen improves sympathetic reinnervation of the proximal urethra. Estrogen titers in individuals with urethral sympathetic nerve damage might, therefore, influence the rate and extent of urethral smooth muscle reinnervation.

Review of: Genetic variation at the CYP19A1 locus predicts circulating estrogen levels but not breast cancer risk in postmenopausal women

Citation of original article:C. A. Haiman, L. Dossus, V. W. Setiawan, D. O. Stram, A. M. Dunning, G. Thomas, M. J. Thun, D. Albanes, D. Altshuler, E. Ardanaz, H. Boeing, J. Buring, N. Burtt, E. E. Calle, S. Chanock, F. Clavel-Chapelon, G. A. Colditz, D. G. Cox, H. S. Feigelson, S. E. Hankinson, R. B. Hayes, B. E. Henderson, J. N. Hirschhorn, R. Hoover, D. J. Hunter, R. Kaaks, L. N. Kolonel, L. Le Marchand, P. Lenner, E. Lund, S. Panico, P. H. Peeters, M. C. Pike, E. Riboli, A. Tjonneland, R. Travis, D. Trichopoulos, S. Wacholder, R. G. Ziegler. Cancer Research 2007; 67(5): 1893–1897.Abstract of the original article:The CYP19A1 gene encodes the enzyme aromatase, which is responsible for the final step in the biosynthesis of estrogens. In this study, we used a systematic two-step approach that included gene resequencing and a haplotype-based analysis to comprehensively survey common genetic variation across the CYP19A1 locus in relation to circulating postmenopausal steroid hormone levels and breast cancer risk. This study was conducted among 5,356 invasive breast cancer cases and 7,129 controls comprised primarily of White women of European descent drawn from five large prospective cohorts within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. A high-density single-nucleotide polymorphism (SNP) map of 103 common SNPs (⩾5% frequency) was used to identify the linkage disequilibrium and haplotype patterns across the CYP19A1 locus, and 19 haplotype-tagging SNPs were selected to provide high predictability of the common haplotype patterns. We found haplotype-tagging SNPs and common haplotypes spanning the coding and proximal 5′ region of CYP19A1 to be significantly associated with a 10% to 20% increase in endogenous estrogen levels in postmenopausal women [effect per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 4.4 × 10(−15)]. No significant associations were observed, however, with these SNPs or common haplotypes and breast cancer risk. Thus, although genetic variation in CYP19A1 produces measurable differences in estrogen levels among postmenopausal women, the magnitude of the change was insufficient to contribute detectably to breast cancer.

The causes of physiological suppression among female meerkats: A role for subordinate restraint due to the threat of infanticide?

In many animal societies, subordinates exhibit down-regulated reproductive endocrine axes relative to those of dominants, but whether this ‘physiological suppression’ arises from active interference by dominants or subordinate self-restraint is a matter of debate. Here we investigate the roles that these processes play in precipitating physiological suppression among subordinate female meerkats, Suricata suricatta. We show that, while subordinate females are known to suffer stress-related physiological suppression during periodic temporary evictions by the dominant female, their low estrogen levels while within their groups cannot be readily attributed to chronic stress, as their fecal glucocorticoid metabolite levels during this time are comparable to those of dominants. The low estrogen levels of subordinate females also cannot be explained simply by self-restraint due to factors that could reduce their payoff from maintaining their fertility regardless of the presence of the dominant female (young age, a lack of unrelated mates, poor body condition and limited breeding experience), as substantial rank-related differences in fecal total-estrogen metabolite levels remain when such factors are controlled. We suggest that this residual difference in estrogen levels may reflect a degree of subordinate restraint due in part to the dominant female's ability to kill their young. Accordingly, subordinate female estrogen levels vary in association with temporal variation in the likelihood of infanticide by the dominant. Attempts to identify the causes of physiological suppression should be cautious if rejecting any role for dominant interference in favor of subordinate restraint, as the dominant's capacity to interfere may often be the reason why subordinates exercise restraint.