Blood Estrogen Levels Research Articles

Intracellular Retention of Estradiol is Mediated by GRAM Domain-Containing Protein ASTER-B in Breast Cancer Cells.

Elevated blood levels of estrogens are associated with poor prognosis in estrogen receptor-positive (ER+) breast cancers, but the relationship between circulating blood hormone levels and intracellular hormone concentrations are not well characterized. We observed that MCF-7 cells treated acutely with 17β-estradiol (E2) retain a substantial amount of the hormone even upon removal of the hormone from the culture medium. Moreover, global patterns of E2-dependent gene expression are sustained for hours after acute E2 treatment and hormone removal. While circulating E2 is sequestered by sex hormone binding globulin (SHBG), the potential mechanisms of intracellular E2 retention are poorly understood. We found that a mislocalization of a steroid-binding GRAM-domain containing protein, ASTER-B, to the nucleus, which is observed in a subset of breast cancer patients, is associated with higher cellular E2 retention. Accumulation and retention of E2 are related to the steroidal properties of E2, and require nuclear localization and steroid binding by ASTER-B, as shown using a panel of mutant ASTER-B proteins. Finally, we observed that nuclear ASTER-B-mediated E2 retention is required for sustained hormone-induced ERalpha chromatin occupancy at enhancers and gene expression, as well as subsequent cell growth responses. Our results add intracellular hormone retention as a mechanism controlling E2-dependent gene expression and downstream biological outcomes. Implications: Mislocalized nuclear ASTER-B, which binds estradiol to support the functions of ER, can provide an alternate means of enhancing the biological effects of E2 in breast cancers and may be a potential therapeutic target that addresses multiple aspects of estrogen bioavailability.

Impact of Letrozole on Prevention of Early Onset Ovarian Hyperstimulation Syndrome in GnRH Antagonist Protocol: A Randomized Controlled Trial

Abstract Background Ovarian hyperstimulation syndrome (OHSS) is a risk associated with assisted reproductive technology. There is a link between higher incidences of OHSS and higher blood estrogen levels. With its strong, targeted, and reversible inhibition of aromatase and E synthetase, the nonsteroidal aromatase inhibitor letrozole can prevent the conversion of androgens into estrogens. Methods Study populations were divided into two equal groups: Group I: Consisted of 85 women who received controlled ovarian stimulation with a conventional antagonist protocol and letrozole. Group II: Consisted of 85 women who received controlled ovarian stimulation with a conventional GnRH antagonist protocol and a placebo. Results There were statistically significant differences among the groups in terms of Estradiol level on Trigger Day (p = 0.037), Number of oocytes retrieved (p = 0.018). The total days of stimulation and cumulative Gonadotropin dose were significantly lower in the Letrozole group (p = 0.045). There were no significant differences between the groups as regard endometrial thickness at trigger day, number of fertilized oocytes, fertilization rate, embryos transferred per cycle, and fresh embryos transferred, mild and critical early onset OHSS, Cycle cancels, Biochemical pregnancy, and Clinical pregnancy between the two groups (P > 0.05). There was a significant difference as regard moderate and severe early onset OHSS between the two groups (P < 0.05). Conclusion We've concluded that for PCOS patients facing a high risk of OHSS, supplementing the GnRH-ant protocol with LE offers a safer, more effective, cost-efficient, and patient-friendly approach compared to the traditional GnRH-ant protocol. The use of LE alongside conventional protocols might alleviate severe forms of OHSS, even among those at extreme risk, without compromising the potential for implantation, pregnancy, and delivery

Phytochemical screening, molecular docking, antifertility investigations, and ADME potential of various extracts of Pandanus odoratissimus leaves.

The purpose of this study was to explore the molecular docking characteristics and antifertility impacts of petroleum ether extract (PEEPO) and chloroform (CHEPO) derived from Pandanus odoratissimus (PO) leaves. TriposSybyl-X 2.1 for molecular docking and Swiss ADME for ADME predictions were used. Antifertility activity was determined by using two invivo animal models, with a focus on estrogenic/antiestrogenic activity and anti-implantation effects. The findings showed that at different doses (100, 200, and 400 mg/kg), PEEPO had more anti-implantation effect than CHEPO. After taking either extract orally for up to 4,000 mg/kg, no acute toxicity was found. Furthermore, both extracts substantially raised blood oestrogen levels while lowering serum cholesterol and LDL levels, improving their antiimplantation and estrogenic activities, whether given alone or in combination with ethinyl estradiol. Molecular docking scores suggested strong interactions between phytochemicals in the extracts and estrogen receptors. ADME studies highlighted four phytochemicals present in PO leaves, showing high gastrointestinal absorption, blood-brain barrier permeability, and negative Log Kp values, indicating their potential as antifertility agents. The phytochemicals in both PEEPO and CHEPO demonstrated promising antifertility potential and interactions with estrogen receptors. Isolation of these phytochemicals could lead to the development of effective herbal antifertility formulations.

Formulation and Evaluation of Herbal Tablets from the Shimshin-6 Prescription and Its Effect on Postpartum Involution in Rats

The Shimshin-6 prescription has been used to treat female patients for blood clots, back and waist pain, and menstrual cramps. It is intended to support the recovery of the uterus after both childbirth and abortion. The purpose of this study is to create a tablet form of the Shimshin-6 formula and examine its effects on the recovery of the uterus after childbirth. The granules were developed using wet granulation, and the tablets were made using a direct compression method. Our test product in tablet form was manufactured following the quality parameters specified in the Mongolian National Pharmacopoeia. Shimshin-3 tablet was considered the best formulation; it used 5% cane sugar as a binder. In this study, Shimshin-6 treatment significantly reduced the uterus index and blood estrogen levels compared to the control group showing no difference in progesterone concentration. We found that Shimshin-6 decreased Tumor Necrosis Factor (TNFα) and regulated growth factors in postpartum rats. Shimshin-6 also regulated postpartum uterine recovery, as indicated by histological analysis. Our results showed the infiltration of inflammatory cell and hemorrhagic changes in the uterine wall. In conclusion, the formulation and evaluation of herbal tablets were satisfactory, and it has been found to enhance uterine recovery postpartum in rats.

The Association between Estrogen Levels and Prostate Volume in Obese and NonObese Benign Prostatic Hyperplasia (BPH) Patients

Objective: To investigate the association between prostate volume and estrogen levels in obese and non-obese individuals suffering from Benign Prostatic Hyperplasia (BPH). Study Design and Setting: Cross-sectional, analytical study Methodology: The International Prostatic Symptom Score (IPSS) was used in the study to recognize sixty participants with BPH. The study examined patients' height, weight, waist circumference (WC), and body mass index (BMI). An IPSS score of less than 7 was seen as healthy. Using standardized BMI (25) and waist circumference (90cm), patients were split into two groups, with obese patients being placed in group A and non-obese patients being placed in group B. Using trans-rectal ultrasonography(TRUS), prostate gland's dimensions were measured, and blood samples were taken to determine serum estrogen levels. Results: In comparison to the non-obesity group, which had a mean prostate volume (PV) of 31.21±6.771 ml, the obese group's PV was 36.13±3.673ml. It was statistically significant that there was a difference between the two groups (p=0.001). In the non-obese group, average level of estrogen was 309.72±73.62pmol/l, compared to 328.21±115.05pmol/l in the obese group (p=0.462). Correlation study (r=0.279,p=0.031) revealed a significantly ideal relationship between participants' blood estrogen levels and PV. Among patients who were obese, there was a significant positive correlation among blood estrogen levels and prostate size(r=0.638, p=0.0001). Conclusion: When compared to the non-obese group, obesity significantly raises prostate volume in study participants, leading to benign prostatic hypertrophy. In addition, prostate volume and blood estrogen levels in obese males showed a significant positive association.

Abstract 756: Differences in composition, diversity, and function of the fecal microbiota of post-menopausal breast cancer patients compared to healthy, age-matched controls

Abstract Gut microbiota are a community of organisms that colonize the intestinal tract with essential roles in immune function, gut epithelial integrity, and metabolite production. Dysbiosis occurs when the gut microbiota environment is negatively altered causing detrimental changes to these functions, which may predispose an individual to breast cancer development. To understand the relationship between dysbiosis and breast cancer development, fecal microbiota samples were collected from 27 post-menopausal breast cancer patients of varying hormone receptor statuses (ER+HER2-, ER+Her2+, ER-HER2+, or ER-Her2-) prior to starting chemotherapeutic treatment. Samples were compared to 25 healthy controls, and all samples underwent 16srRNA sequencing. Samples from breast cancer patients and control groups were compared for significant differences (P<.05) in alpha (within sample) and beta (between sample) diversity. Using the Shannon Index and Generalized Least Squares Model, significant differences in alpha diversity were identified between all breast cancer types vs. controls (P=.0104), and between ER+HER2- breast cancer vs. controls (P=.00153). Healthy controls exhibited a higher mean Shannon Index than breast cancer patients, thus higher within sample diversity. Using principal coordinate analyses, significant differences in beta diversity were identified between all breast cancer types vs. controls (P = .01199), and ER+HER2- breast cancer vs. control (P = .008991). Further analyses identified significant taxa of microbiota with functions related to breast cancer development and progression. Of note, Lachnoclostridium, a genus of bacteria that can produce β-glucuronidase, which can deconjugate estrogen, was increased in all breast cancer types and ER+HER2- breast cancer when compared to controls. Deconjugation of estrogen can cause elevated blood estrogen levels, potentially increasing Estrogen Receptor binding in hormone-receptor-positive breast cancer. Additionally, Akkermansia, a genus implicated in gut barrier dysfunction, was decreased in ER+HER2- patients, while Parvimonas, a tumorigenic cell-cycle regulator, was increased. Elucidating if these effects are causative or reactionary may have important implications for understanding breast cancer etiology. Samples are currently undergoing additional metagenomic analyses using long-read sequencing to identify specific bacteria, viruses, fungi, parasites, and phages that may be contributing to dysbiosis. Overall, this study is the first, to our knowledge, to employ short and long-read sequencing to the fecal samples of untreated postmenopausal breast cancer patients. We provide mechanistic insight into the relationship between microbiota and breast cancer development, with the intent of informing future patient screening and prevention. Citation Format: Nadia Kabbej, Frederick Ashby, Erika Atencio, Erinn Rosenkrantz, Dominique Day, Khloe Dang, Josee Gauthier, Rachel Newsome, John Sommerville, Taqwa Naas, Raad Gharaibeh, Christian Jobin, Amira Quevedo, Coy D. Heldermon. Differences in composition, diversity, and function of the fecal microbiota of post-menopausal breast cancer patients compared to healthy, age-matched controls [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 756.

17β-Estradiol Effects in Skeletal Muscle: A 31P MR Spectroscopic Imaging (MRSI) Study of Young Females during Early Follicular (EF) and Peri-Ovulation (PO) Phases

The natural variation in estrogen secretion throughout the female menstrual cycle impacts various organs, including estrogen receptor (ER)-expressed skeletal muscle. Many women commonly experience increased fatigue or reduced energy levels in the days leading up to and during menstruation, when blood estrogen levels decline. Yet, it remains unclear whether endogenous 17β-estradiol, a major estrogen component, directly affects the energy metabolism in skeletal muscle due to the intricate and fluctuating nature of female hormones. In this study, we employed 2D 31P FID-MRSI at 7T to investigate phosphoryl metabolites in the soleus muscle of a cohort of young females (average age: 28 ± 6 years, n = 7) during the early follicular (EF) and peri-ovulation (PO) phases, when their blood 17β-estradiol levels differ significantly (EF: 28 ± 18 pg/mL vs. PO: 71 ± 30 pg/mL, p < 0.05), while the levels of other potentially interfering hormones remain relatively invariant. Our findings reveal a reduction in ATP-referenced phosphocreatine (PCr) levels in the EF phase compared to the PO phase for all participants (5.4 ± 4.3%). Furthermore, we observe a linear correlation between muscle PCr levels and blood 17β-estradiol concentrations (r = 0.64, p = 0.014). Conversely, inorganic phosphate Pi and phospholipid metabolite GPC levels remain independent of 17β-estradiol but display a high correlation between the EF and PO phases (p = 0.015 for Pi and p = 0.0008 for GPC). The robust association we have identified between ATP-referenced PCr and 17β-estradiol suggests that 17β-estradiol plays a modulatory role in the energy metabolism of skeletal muscle.

3D hotspot engineering and analytes strategy enabled ultrasensitive SERS platform for biosensing of depression biomarker

Nowadays, the diagnose of depression mainly relies on clinical examination while impossible to accurately evaluate the occurrence of depression. Chemical approaches are captivating to analyze stress biomarkers for feedbacking body's endocrine response to stress stimuli. However, it remains challenging in exploring accurate, reliable and sensitive approaches. Herein, we rationally design a newly SERS platform with integrated hotspots engineering and analyte strategy to achieve highly sensitive analysis for estrogen, a typical depression biomarker in adolescent female. On the one hand, the 3D micro/nano plasmonic substrate containing Au–Ag Alloy Nanourchins (AAA-NUs) and arrays-based monolayer films of Au nanoparticles (Au NSs) was constructed to achieve high density and availability of hotspots. On the other hand, the analyte strategy was designed via rapid azotizing reaction to further enhance the scattering cross-section of estrogen in the form of azido compounds. With the synergism of them, the proposed SERS platform displayed high sensitivity for estrogen with a limit of detection down to 10−11 mg/mL. More importantly, the blood estrogen levels of depressed patients were evaluated via the proposed SERS platform and presented high consistence with clinical diagnostic results. This integrated SERS platform paves the way for universal and ultrasensitive biosensing and possess great potential for applying in multi-target detection and disease prediction.

Radiomic features of the hippocampal based on magnetic resonance imaging in the menopausal mouse model linked to neuronal damage and cognitive deficits

Estrogen deficiency in the early postmenopausal phase is associated with an increased long-term risk of cognitive decline or dementia. Non-invasive characterization of the pathological features of the pathological hallmarks in the brain associated with postmenopausal women (PMW) could enhance patient management and the development of therapeutic strategies. Radiomics is a means to quantify the radiographic phenotype of a diseased tissue via the high-throughput extraction and mining of quantitative features from images acquired from modalities such as CT and magnetic resonance imaging (MRI). This study set out to explore the correlation between radiomics features based on MRI and pathological features of the hippocampus and cognitive function in the PMW mouse model. Ovariectomized (OVX) mice were used as PWM models. MRI scans were performed two months after surgery. The brain’s hippocampal region was manually annotated, and the radiomic features were extracted with PyRadiomics. Chemiluminescence was used to evaluate the peripheral blood estrogen level of mice, and the Morris water maze test was used to evaluate the cognitive ability of mice. Nissl staining and immunofluorescence were used to quantify neuronal damage and COX1 expression in brain sections of mice. The OVX mice exhibited marked cognitive decline, brain neuronal damage, and increased expression of mitochondrial complex IV subunit COX1, which are pathological phenomena commonly observed in the brains of AD patients, and these phenotypes were significantly correlated with radiomics features (p < 0.05, |r|>0.5), including Original_firstorder_Interquartile Range, Original_glcm_Difference Average, Original_glcm_Difference Average and Wavelet-LHH_glszm_Small Area Emphasis. Meanwhile, the above radiomics features were significantly different between the sham-operated and OVX groups (p < 0.01) and were associated with decreased serum estrogen levels (p < 0.05, |r|>0.5). This initial study indicates that the above radiomics features may have a role in the assessment of the pathology of brain damage caused by estrogen deficiency using routinely acquired structural MR images.

Does in vitro fertilization affect the hearing levels of women?

This study aimed to determine whether there is a relationship between changes in blood estrogen levels and hearing threshold levels in women undergoing in vitro fertilization (IVF). Sixty patients with normal otoscopic examination findings and scheduled for IVF treatment were included in the study. All patients underwent pure tone audiometry, tympanogram tests, and otoacoustic emission measurements (TEOAE) during IVF treatment, and estrogen levels were measured simultaneously. The patients were divided into three groups based on estrogen levels during IVF. The patients' audiological test results at the beginning and end of treatment (the 12th day) were compared between the groups. There was an increase in hearing levels on the 12th day of treatment compared to the beginning of treatment in all the study groups. This increase was significant between Group 1 and Group 2 and between Group 1 and Group 3 (p<0.05). The best hearing in audiometry was determined in the patients in Group 2. While a significant increase was observed in TEOAE (otoacoustic emission) measurements in Groups 1 and 2, a significant decrease was determined in Group 3 (p<0.05). Middle ear pressure and compliance measurements on the tympanogram tests were significantly lower in Group 3 compared to Groups 1 and 2 (p<0.05). During IVF treatment, as the estrogen level increases, it causes an increase in the level of hearing, but this increase does not continue after specific doses.

Fenugreek Seed Ethanolic Extract Improves Alveolar Bone Parameters by Attenuating Inflammation in Ovariectomized Rats.

Alveolar bone residual ridge resorption remains a major challenge for dental implant placement in patients with edentulism. Fenugreek seed extracts have been reported to have potential roles in bone metabolism. This study aimed to evaluate the effects of fenugreek seed ethanolic extract (FSEE) on bone cells, inflammation, hormones, and angiogenesis parameters of alveolar bone tissue following teeth extraction in an ovariectomized (OVX) model. A total of 30 adults female Wistar rats were assigned into two major groups. Each group consisted of control, OVX, OVX+FSEE 100 mg/kg BW, OVX+FSEE 200 mg/kg BW, and OVX+FSEE 400 mg/kg BW. The FSEE treatment was applied through the intragastric route for 7 days in the first group and for 30 days in the second group of animals. The first molar tooth of the right maxilla was extracted before the FSEE treatment. The level of 17β-estradiol was measured by the ELISA method. The dissected maxilla alveolar bone processus was sectioned for histological evaluation by hematoxylin-eosin staining and an immunohistochemistry assay. This study found that FSEE reduced the blood estrogen level and increased estrogen receptor-α (ER-α) expression. FSEE administration modified the number of bone cells, angiogenesis, vascular endothelial growth factor (VEGF), sclerostin, and the osteoprotegerin/receptor activator of nuclear factor kappa-β ligand (OPG/RANKL) ratio. Alterations were seen in the inflammatory markers interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), and the macrophage-1/macrophage-2 (M1/M2) ratio. In this study, inflammation was found to be attenuated by reductions in IL-6 and sclerostin, and an increase in TGF-β1. The maturation of bone osteocytes increased along with the increase in ER-α expression and ratio of OPG/RANKL.

Association of serum cortisol and cortisone levels and risk of recurrence after endocrine treatment in breast cancer

Metabolic reprogramming in breast cancer involves changes in steroid hormone synthesis and metabolism. Alterations in estrogen levels in both breast tissue and blood may influence carcinogenesis, breast cancer growth, and response to therapy. Our aim was to examine whether serum steroid hormone concentrations could predict the risk of recurrence and treatment-related fatigue in patients with breast cancer. This study included 66 postmenopausal patients with estrogen receptor-positive breast cancer who underwent surgery, radiotherapy, and adjuvant endocrine treatment. Serum samples were collected at six different time points [before the start of radiotherapy (as baseline), immediately after radiotherapy, and then 3, 6, 12 months, and 7–12 years after radiotherapy]. Serum concentrations of eight steroid hormones (cortisol, cortisone, 17α-hydroxyprogesterone, 17β-estradiol, estrone, androstenedione, testosterone, and progesterone) were measured using a liquid chromatography–tandem mass spectrometry-based method. Breast cancer recurrence was defined as clinically proven relapse/metastatic breast cancer or breast cancer-related death. Fatigue was assessed with the QLQ-C30 questionnaire. Serum steroid hormone concentrations measured before and immediately after radiotherapy differed between relapse and relapse-free patients [(accuracy 68.1%, p = 0.02, and 63.2%, p = 0.03, respectively, partial least squares discriminant analysis (PLS-DA)]. Baseline cortisol levels were lower in patients who relapsed than in those who did not (p < 0.05). The Kaplan–Meier analysis showed that patients with high baseline concentrations of cortisol (≥ median) had a significantly lower risk of breast cancer recurrence than patients with low cortisol levels (<median) (p = 0.02). During follow-up, there was a decrease in cortisol and cortisone concentrations in relapse-free patients, whereas these steroid hormones increased in patients who relapsed. In addition, steroid hormone concentrations immediately after radiotherapy were associated with treatment-related fatigue (accuracy of 62.7%, p = 0.03, PLS-DA). However, baseline steroid hormone levels did not predict fatigue at 1 year or at 7–12 years. In conclusion, breast cancer patients with low baseline cortisol levels were more likely to experience recurrence. During follow-up, cortisol and cortisone levels decreased in relapse-free patients but increased in patients with recurrence. Thus, cortisol and cortisone may act as potential biomarkers indicating individual risk of recurrence.

BDNF promotes mouse follicular development and reverses ovarian aging by promoting cell proliferation

BackgroundBrain-derived neurotrophic factor (BDNF) plays an important role in ovarian function including follicle development and oocyte maturation, and embryonic development. However, whether BDNF treatment can reimpose ovarian aging and impaired fertility remains elusive. In this study, we investigated the reproductive outcomes of BDNF treatment and potential mechanisms in aged mice.Method“Aged” mice (35–37 weeks old, n = 68) were treated with recombinant human BDNF protein (rhBDNF, 1 µg/200 µL) through daily intraperitoneal (IP) injection for 10 days with/without ovulation induction. Reproductive age mice (8–10 weeks old, n = 28) were treated with ANA 12 (a selective BDNF receptor, TrkB antagonist) through daily IP injection for 5 days with/without ovulation induction. Ovarian function was assessed by ovarian weight, number of follicles, and sex hormone productions. Following induction of ovulation, the number of total oocytes or abnormal oocytes, and blastocyst formation were assessed. Reproductive functions of the mice were evaluated, including pregnancy rate, mating duration for conception, implantation sites, litter size, and weight of offspring. Finally, the molecular mechanism of the effects of BDNF on ovarian cell functions in mice were examined by Western blot and immunofluorescence.ResultsrhBDNF treatment increased the ovarian weight, number of follicles, number and quality of oocytes including increased blastocysts formation, blood estrogen levels, and pregnancy rate in 35-37-week-old mice. Conversely, BDNF receptor antagonist, ANA 12, treatment decreased the ovarian volume and number of antral follicles and increased the proportion of abnormal oocytes in 8-10-week-old mice. We further demonstrated that BDNF treatment promoted ovarian cell proliferation as well as activation of TrkB and cyclinD1-creb signalling.ConclusionWe demonstrated that ten consecutive days of daily IP injection of rhBDNF rescued ovarian function in aged mice. Our results further indicate that TrkB and cyclin D1-creb signaling may underlie the BDNF function in ovaries. Targeting BDNF-TrkB signaling is a potential novel therapeutic strategy to reverse ovarian aging.

IPSCs-derived mesenchymal stromal cells mitigate anxiety and neuroinflammation in aging female mice.

Perimenopause is a natural transition to menopause, when hormone disturbance can result in both short-term mental disorders, such as anxiety, and long-term neuroinflammation due to blood-brain barrier (BBB) impairment, which may lead to more serious neurological disorders later on, such as dementia. Effective treatments may prevent both short-term and long-term neurological sequela, which formed the aim of this study. In aged female C57BL/6 mice (16-18 months of age), mesenchymal stromal cells (MSCs) differentiated from human-induced pluripotent stem cells (iPSCs), were administered via tail vein injection. Mice showed increased blood estrogen levels, alleviated anxiety and neuroinflammation, and improved BBB integrity. Interestingly, transplanted MSCs were located close to ovarian sympathetic nerves and decreased ovarian norepinephrine levels, which in turn increased ovarian estrogen secretion. Moreover, the administration of anastrozole, an inhibitor of estrogen synthesis, diminished the therapeutic effects of MSCs in vivo, suggesting the effect to be estrogen-dependent. In vitro study confirmed the impact of MSCs on sympathetic nerves via mitochondria exchange. In conclusion, iPSC-derived MSCs may provide a novel option to manage perimenopause-related hormonal dysregulation and neurological disorders during the female aging process.

Ethanol potentiates follicle-stimulating hormone action in ovarian granulosa cells.

There are many previous reports on the effects of ethanol on physiological function, including reports of elevated blood estrogen levels in women who drank alcohol. However, the mechanism of ethanol's effects on ovarian functions, such as follicle development and hormone secretion, has not been fully clarified. Therefore, in this study, we investigated the impacts of ethanol on these phenomena and their mechanisms using a primary culture system of rat ovarian granulosa cells (GCs). In the present experiment, groups were created in which follicle-stimulating hormone (FSH) or ethanol was added alone or FSH and ethanol were co-added, and mRNA and protein expression in each group was measured for luteinizing hormone receptor (LHR) and sex steroid hormone synthase, as well as for estradiol (E2) production, cAMP production, and FSH receptor (FSHR) internalization rate. The addition of FSH induced mRNA expression of LHR and aromatase, which led to membrane LHR expression and E2 production. The coexistence of ethanol enhanced all these responses. The action of FSH is exerted via cAMP, and the co-addition of ethanol enhanced this cAMP production. Ethanol alone did not induce cAMP production. The enhancing effect of ethanol was also observed for cAMP induced by cholera toxin. Ethanol had no significant effect on the internalization rate of FSHR. In conclusion, ethanol increased FSH-stimulated cAMP production by increasing the activity of adenylyl cyclase, which enhanced FSH actions in rat GCs. Alcohol is an exacerbating factor in several female hormone-related diseases, and the mechanism of ethanol-induced increase in estrogen secretion revealed in this study may be involved in the pathogenesis of these diseases.

Outcomes of frozen embryo transfer in patients with and without ovarian hyperstimulation syndrome

"Introduction: One of the methods utilized to treat infertility is the use of frozen embryos. This technique is particularly employed in patients with ovarian hyperstimulation syndrome (OHSS), which leads to heightened blood estrogen levels. The purpose of this study was to compare the percentage of pregnancy and abortion between patients who used the frozen embryo method due to OHSS and others who practiced the same method for other reasons. Materials and Methods: This retrospective, cohort study was conducted on a total of 338 patients who visited in vitro fertilization (IVF) section of Kowsar Hospital of Urmia-Iran to employ the frozen embryo method (May 2013 to December 2015). The patients were classified into two groups, i.e. the OHSS group (N=150) and the non-OHSS group (N=188). Data were obtained and examined by evaluating the files in a questionnaire. Results: The two groups did not differ significantly with regard to their mean age (p = 0.57). There was also no statistically significant difference between the OHSS and non-OHSS groups regarding the quality of frozen embryo transferred (P = 0.17). Also, there was also no statistically significant difference between the two groups in terms of their pregnancy rate (OHSS = 30.0% vs. non-OHSS = 25.0%) and miscarriage rate (OHSS = 31.11% vs. non-OHSS = 24.44%) (p = 0.32 and p = 0.31, respectively). Conclusion: Ovum exposure to high estrogen during ovulation stimulation does not affect embryo implantation and miscarriage in patients with OHSS."

Ultrasensitive Quantification of Multiple Estrogens in Songbird Blood and Microdissected Brain by LC-MS/MS

Neuroestrogens are synthesized within the brain and regulate social behavior, learning and memory, and cognition. In song sparrows, Melospiza melodia, 17β-estradiol (17β-E2) promotes aggressive behavior, including during the nonbreeding season when circulating steroid levels are low. Estrogens are challenging to measure because they are present at very low levels, and current techniques often lack the sensitivity required. Furthermore, current methods often focus on 17β-E2 and disregard other estrogens. Here, we developed and validated a method to measure four estrogens [estrone (E1), 17β-E2, 17α-estradiol (17α-E2), estriol (E3)] simultaneously in microdissected songbird brain, with high specificity, sensitivity, accuracy, and precision. We used liquid chromatography tandem mass spectrometry (LC-MS/MS), and to improve sensitivity, we derivatized estrogens using 1,2-dimethylimidazole-5-sulfonyl-chloride (DMIS). The straightforward protocol improved sensitivity by 10-fold for some analytes. There is substantial regional variation in neuroestrogen levels in brain areas that regulate social behavior in male song sparrows. For example, the auditory area NCM, which has high aromatase levels, has the highest E1 and 17β-E2 levels. In contrast, estrogen levels in blood are very low. Estrogen levels in both brain and circulation are lower in the nonbreeding season than in the breeding season. This technique will be useful for estrogen measurement in songbirds and potentially other animal models.

The Relationship Between Sex Hormones, Immune Response and Productive Performance of Broiler Chickens

Numerous researchers hypothesized that testosterone had a "double-edged sword" effect, encouraging the development of secondary sexual features which are thought to be a healthy signal, while also suppressing immunological function. The relationship between external appearance of birds and its immune performance was little approached. The relationship between sex hormones, immune response and productive performance of males and females broiler were evaluated in this work. One day old chicks were sexed and chicks of each sex were randomly distributed into three experimental treatments, 1. TAM20 treatment chicks were supplied with estrogenic antagonist tamoxifen citrate at a dose of 20mg/kg body weight through oral administration; 2. Androgen treatment chicks were injected intramuscularly with synthetic veterinary androgen (Boldenone Undecylenate 50mg) at a dose of 1cm/ 10kg body weight and 3. The control treatment. Tamoxifen and androgen supplementation had no significant effects on final body weight, weight gain, or feed conversion ratio (at 45 days), although the androgen treatment had the significantly highest feed intake and the TAM20 treatment had the lowest. Moreover, differences between males and females for final body weight, weight gain, feed intake and feed conversion ratio were not significant. Androgen injection increased breast percentage significantly compared to TAM20 treatment and numerically compared to control treatment. Also, Androgen supplementation increased significantly comb percentage; however TAM20 decreased it significantly compared to control. Concerning the effects of both treatments on level of sex hormones, androgen showed favorable effects on both testosterone and estrogen when compared to Tamoxifen 20 treatment. On the other hand, administration of TAM 20 improves phagocytic activity as compared to androgen administration. Phagocytic index, productive performance, and carcass traits did not substantially associated with either testosterone and or estrogen blood levels.

Stomach secretes estrogen in response to the blood triglyceride levels

Mammals receive body energy information to maintain energy homeostasis. Ghrelin, insulin, leptin and vagal afferents transmit the status of fasting, blood glucose, body fat, and food intake, respectively. Estrogen also inhibits feeding behavior and lipogenesis, but increases body fat mass. However, how blood triglyceride levels are monitored and the physiological roles of estrogen from the perspective of lipid homeostasis remain unsettled. Here, we show that stomach secretes estrogen in response to the blood triglyceride levels. Estrogen-secreting gastric parietal cells predominantly use fatty acids as an energy source. Blood estrogen levels increase as blood triglyceride levels rise in a stomach-dependent manner. Estrogen levels in stomach tissues increase as blood triglyceride levels rise, and isolated gastric gland epithelium produces estrogen in a fatty acid-dependent manner. We therefore propose that stomach monitors and controls blood triglyceride levels using estrogen, which inhibits feeding behavior and lipogenesis, and promotes triglyceride uptake by adipocytes.

Why the olfactory acuity to Exaltolide test is different in women?

Background Sporadic studies have revealed that sensitivity to Exaltolide depends on the estrogen blood levels in women. Aim comparing the sensitivity to Exaltolide to levels of estrogen in women. Method A total of 60 women were prospectively tested for both sensitivity to Exaltolide and blood estradiol during the menstrual cycle, pregnancy and menopause. Results The average score of sensitivity to Exaltolide was 1.2 during menstruation, 4.8 during proliferative phase, 5.8 at ovulation and 2.4 during the luteal phase. In pregnant women, it was 3.6 during the first trimester, 4.7 during the second and 6 during the third trimester. In post-menopausal women, the average score was 0.3. The average estradiol blood level in pg/ml was 42 during menstruation, 207 during proliferative phase, 368 at ovulation and 147 during the luteal phase. In pregnant women, it was 2506 during the first trimester, 5913 during the second and 9968 during the third trimester. The average estradiol blood level during menopause was 14 pg/ml. The higher the levels of estrogen, the higher sensitivity to Exaltolide. Our results were similar to the findings of previous authors. Conclusion In addition to its common use in perfumery, the odor of Exaltolide could be used as a clinical test of estrogen.