Estradiol Research Articles

English

BACKGROUND Due to the higher prevalence of dry eye disease (DED) in postmenopausal women, it is essential to understand the effects of sex hormones on the ocular surface. This study was done to identify the association between serum concentration of 17 beta estradiol E2 and DED in postmenopausal women. METHODS Our study population comprised of 100 postmenopausal women who were segregated into two groups – 50 symptomatic participants in dry eye group and 50 asymptomatic participants in normal eye group (NEG), based on the dry eye questionnaire assessment. Other preliminary tests to detect DED and meibomian gland dysfunction (MGD) such as tear break up time (TBUT), meibum evaluation, ocular staining score (OSS) and Schirmer’s test were performed. All participants underwent venous sampling for measurement of serum concentration of 17 beta estradiol E2. RESULTS 82 % of participants of DEG belonged to older age group (> 60 years) on comparison with NEG (32 %). A shorter TBUT of 5.78 and 5.96 in DEG as compared to 13.44 and 13.08 in NEG were documented in right and left eyes respectively. Mean serum estradiol was significantly higher in DEG (30.90 pg/ml) than in NEG (16.02 pg/ml). With an increase in the severity of MGD stage, an analogous increase in serum estradiol was noted, which was statistically significant (P < 0.001). CONCLUSIONS Higher levels of serum estradiol correspond with higher stages of MGD, suggesting that sex hormone induced alteration of meibomian gland morphology and function plays an important role in postmenopausal DED. KEY WORDS Dry Eye Disease, Meibomian Gland Dysfunction, 17 Beta Estradiol E2, Postmenopausal Women

The protective effects of 17-β estradiol and SIRT1 against cardiac hypertrophy: a review.

One of the major causes of morbidity and mortality worldwide is cardiac hypertrophy (CH), which leads to heart failure. Sex differences in CH can be caused by sex hormones or their receptors. The incidence of CH increases in postmenopausal women due to the decrease in female sex hormone 17-β estradiol (E2) during menopause. E2 and its receptors inhibit CH in humans and animal models. Silent information regulator 1 (SIRT1) is a NAD+-dependent HDAC (histone deacetylase) and plays a major role in biological processes, such as inflammation, apoptosis, and oxidative stress responses. Probably SIRT1 because of these effects, is one of the main suppressors of CH and has a cardioprotective effect. On the other hand, estrogen and its agonists are highly efficient in modulating SIRT1 expression. In the present study, we review the protective effects of E2 and SIRT1 against CH.

DOES PROLONGED ESTRACE ADMINISTRATION EFFECT ON PREGNANCY OUTCOME IN PROGRAMMED FROZEN EMBRYO TRANSFER CYCLE?

To determine whether women in frozen-thawed embryo transfer (FET) cycles, who continued prolonged estrogen administration beyond the standard 12 days due to a thin endometrial stripe exhibited lower pregnancy rates. We retrospectively analyzed the outcomes of 822 FET cycles from January 1, 2019 through March 1, 2021. Oocyte recipients or women with known intrauterine adhesions were excluded. Women received twelve days of 6 mg of oral 17 beta Estradiol (Estrace) after ovarian suppression was confirmed. If after twelve days of Estrace their endometrial stripe (ES) was equal to or less than 7 mm, then their estrogen regimen was continued until her ES was at least 7mm. Intramuscular progesterone 50mg intramuscularly was then administered and a single thawed blastocyst was transferred 132 hours later. Variables assessed included thickens of endometrium, pregnancy (serum hCG), clinical pregnancy, and implantation rate by fetal cardiac activity and pregnancy outcome. The Fisher’s Exact Test and t-test were used. A p value <0.05 was considered significant. Twenty three of 822 cycle were continued on their estrogen regimen to meet ES criteria for at least five days (range 5 to 14 days). No significant differences in age, prior failed FET cycles, and percentage of euploid blastocysts were noted between those women who did or did not requires at least five days more of exogenous estrogen. However, endometrial thickness was significantly thicker in regular FET group compared that of pushed FET cycle at day 12 (9.59 mm vs 6.16 mm, p<0.05). Furthermore, their thin endometrial thickness was significantly improved after prolonged Estrace (6.16 mm vs 7.49 mm, p<0.05). Among pushed FET cycles, five patients were pushed for 14 days and the endometrial thickness were improved from 4.78 mm to 7.08 mm (p=0.11). The pregnancy rate (positive serum hCG/total transfers), clinical pregnancy rates and implantation rate were not significantly different between regular and pushed FET cycles (73.2 %vs 75.0 %), (68.8 % vs 62.5 %), and (59.4 % vs 52.0 %), respectively. The pregnancy outcomes in two groups were similar by age group or PGT performed group. Additionally, chemical pregnancy loss or miscarriage rate did not differ between two groups (7 % vs 4%) and (7 % vs 4 %), respectively. Ongoing pregnancy/live birth rate was 60.9 % (14/23) for regular FET and 59.7 % (462/799) for pushed FET. Our findings suggest that continued exogenous estrogen administration successfully increased the endometrial thickness in all patients with a thin ES and did not adversely affect pregnancy outcome.

G protein‐coupled estrogen receptor‐1 enhances excitatory synaptic responses in the entorhinal cortex

Activation of estrogen receptors is thought to modulate cognitive function in the hippocampus, prefrontal cortex, and striatum by affecting both excitatory and inhibitory synaptic transmission. The entorhinal cortex is a major source of cortical sensory and associational input to the hippocampus, but it is unclear whether either estrogens or progestogens may modulate cognitive function through effects on synaptic transmission in the entorhinal cortex. This study assessed the effects of the brief application of either 17-β estradiol (E2) or progesterone on excitatory glutamatergic synaptic transmission in the female rat entorhinal cortex in vitro. Rats were ovariectomized on postnatal day (PD) 63 and also received subdermal E2 implants to maintain constant low levels of circulating E2 on par with estrus. Electrophysiological recordings from brain slices were obtained between PD70 and PD86, and field excitatory postsynaptic potentials (fEPSPs) reflecting the activation of the superficial layers of the entorhinal cortex were evoked by the stimulation of layer I afferents. The application of E2 (10nM) for 20 min resulted in a small increase in the amplitude of fEPSPs that reversed during the 30-min washout period. The application of the ERα agonist propylpyrazoletriol (PPT) (100 nM) or the β agonist DPN (1μM) did not significantly affect synaptic responses. However, the application of the G protein-coupled estrogen receptor-1 (GPER1) agonist G1 (100 nM) induced a reversible increase in fEPSP amplitude similar to that induced by E2. Furthermore, the potentiation of responses induced by G1 was blocked by the GPER1 antagonist G15 (1μM). Application of progesterone (100 nM) or its metabolite allopregnanolone (1μM) did not significantly affect synaptic responses. The potentiation of synaptic transmission in the entorhinal cortex induced by the activation of GPER1 receptors may contribute to the modulation of cognitive function in female rats.

Factors associated with xerostomia in perimenopausal women.

Various oral symptoms, including xerostomia and burning mouth syndrome, may occur in menopausal women. These symptoms reduce quality of life (QOL). However, the actual condition of xerostomia after menopause is not clear. The purpose of this study was to reveal the factors associated with xerostomia in perimenopausal women. Participants included 118 outpatients (mean age, 49.9 ± 3.2 years; range, 45-55 years) at a department of gynecology in Japan. Information was collected concerning age, medical history, medications, menstrual status, and history of treatment for climacteric symptoms. Oral symptoms, including xerostomia were evaluated with a 3-point scale. The climacteric symptom checklist for Japanese women and 36-Item Short-Form Health were used to evaluate climacteric symptoms and QOL, respectively. In addition, the volume of unstimulated saliva, oral moisture, salivary α-amylase, chromogranin A, and 17-β estradiol were measured. Higher age, the total number of medications, psychotropic drug, hormone replacement therapy, treatment for climacteric symptoms, sticky mouth, burning sensation of tongue, dryness of nose and 14 of the 21 climacteric symptoms significantly affected xerostomia. In addition, treatment for climacteric symptoms, fall asleep but often awake at night, headaches and dryness of nose were significantly associated with xerostomia. In conclusion, xerostomia is closely associated to factors such as treatment for climacteric symptoms and certain menopausal symptoms, and it may be related to QOL in perimenopausal women.

Inflammatory repercussions in female steroid responsive glands after perinatal exposure to bisphenol A and 17-β estradiol.

The mammary gland (MG) and female prostate are plastic reproductive organs which are highly responsive to hormones. Thus, endocrine disruptors, such as bisphenol A (BPA) and exogenous estrogens, negatively affect glandular homeostasis. In addition to previously described alterations, changes in inflammatory markers expression also trigger the development of a microenvironment that contributes to tumor progression. The current work aimed to evaluate the inflammatory responses of the MG and prostate gland to BPA (50 µg/kg) and 17-β estradiol (35 µg/kg) exposure during the perinatal window of susceptibility. The results showed that at 6 months of age there was an increase in the number of phospho-STAT3 (P-STAT3) positive cells in the female prostate from animals perinatally exposed to 50 µg/kg BPA daily. In addition, the number of macrophages increased in these animals in comparison with nonexposed animals, as shown by the F4/80 marker. Despite an increase in the incidence of lobuloalveolar and intraductal hyperplasia, the MG did not show any difference in the expression of the four inflammatory markers evaluated: tumor necrosis factor-α, COX-2, P-STAT3, and F4/80. Analysis of both glands from the same animal led to the conclusion that exposure to endocrine disruptors during the perinatal window of susceptibility leads to different inflammatory responses in different reproductive organs. As the prostate is more susceptible to these inflammatory mechanisms, it is reasonable to affirm that possible neoplastic alterations in this organ are related to changes in the inflammatory pattern of the stroma, a characteristic that is not evident in the MG.

17-β estradiol signalling affects cardiovascular and cancer pathogenesis by regulating the crosstalk between transcription factors and EC-miRNAs

17β-estradiol (E2) or the bioactive form of estrogen has wide range of impact in regulating human physiology. It not only regulates organ development but also controls immune responses. E2 impacts the recruitment of immune cells to endothelium by regulating the expression of pattern recognition receptors. As endothelium is central to human physiology, it becomes a good target for many cancer and cardiovascular diseases. A broad range of genes get dysregulated during the course of pathophysiological events and many of them are regulated via E2 signalling. Recent evidence shows that E2 regulate the expression of many endothelial cell specific microRNAs (EC-miRNA), thereby affecting expression and stability of many factors including estrogen receptor alpha. In this study, we analysed two distinct datasets of different endothelial cell models to discern a set of genes that potentially play very crucial role in regulating general physiological as well as pathophysiological events. GEO2R and Cytoscape were used to analyze the datasets GSE51535 and GSE16683. DAVID and ClueGO functional annotation of the genes revealed association with genetically associated disease classes such as cancer and cardiovascular. KEGG pathways, Reactome pathways and Wiki-pathways were used for pathway enrichment analysis. One of the enriched pathways includes the synthesis of pri-miRNA by RNA polymerase II. Endothelial cell specific miRNA and target gene association revealed key miRNAs and their involvement in regulatory pathways. Overall, our study highlights the complexity of miRNA mediated E2 regulation of genes in endothelial cells and provides potential target genes for therapeutics in cancer and cardiovascular pathophysiological conditions.

Species validation, growth, reproduction and nutritional perspective of Indian pompano, Trachinotus mookalee–A candidate species for diversification in coastal mariculture

The Indian pompano Trachinotus mookalee can be an ideal and alternative marine candidate species for aquaculture with its cultivable traits. The study aimed to understand growth, reproductive and nutritional potentials of the fish in different culture environments and also for species validation to avoid ambiguities in further research. Wild collected broodfishes have confirmed that the species is genetically and morphologically differentiated from its four closely related species of genus Trachinotus. The studied fish growth was significantly (P < 0.05) influenced by culture environments, where the maximum growth was attained in cage (684.9 ± 14.0 g), followed by pond (564 ± 13.6 g), Recirculating Aquaculture System (RAS) (471.5 ± 10 g) and the least in indoor Fibre-reinforced plastic tank (294.65 ± 10.35 g) for 12 months of culture. Growth data indicated presence of high genetic growth potential in the species, which could be improved with suitable intervention in abiotic factors. Studied reproductive sex steroid hormone concentrations varied in the fish and were matched with the different maturity stages confirmed by gonadal development stages. The sexually mature male and female fish found with elevated levels of testosterone (2.34 ± 0.25 ng/ml) and 17-β estradiol (2.56 ± 0.95 ng/ml), respectively, which indicated that sex differences has been persisting in the species and the steroid level could act as marker in assessing the maturity status of male and female fish. The gonadal developmental stages indicated that the fish became functional male and female brooders after 26 and 29 months of culture in sea cages, respectively. Nutritional contents of the fish was significantly (P < 0.05) influenced by the culture environments. Crude protein was maximum in cage reared fish (18.96 ± 0.36%), whereas fish in RAS exhibited high crude fat (6.87 ± 1.05%). Palmitic (C16:0) and glutamic acids were the maximum abundant fatty acid and amino acid, respectively in all the cultured environments. However, the content of essential polyunsaturated fatty acids (DHA and EPA) was significantly high in wild fish. Phosphorus and iron were the maximum abundant major and micro minerals, respectively in all the culture systems. With excellent traits linked with aquaculture, the species could be the most suitable candidate for species diversification in coastal mariculture. The species deserves further studies on the basis of influence of abiotic factors on different traits.

Anti-Apoptotic and Antioxidant Activities of the Mitochondrial Estrogen Receptor Beta in N2A Neuroblastoma Cells.

Estrogens are steroid hormones that play a crucial role in the regulation of the reproductive and non-reproductive system physiology. Among non-reproductive systems, the nervous system is mainly affected by estrogens due to their antioxidant, anti-apoptotic, and anti-inflammatory activities, which are mediated by membranous and nuclear estrogen receptors, and also by non-estrogen receptor-associated estrogen actions. Neuronal viability and functionality are also associated with the maintenance of mitochondrial functions. Recently, the localization of estrogen receptors, especially estrogen receptor beta, in the mitochondria of many types of neuronal cells is documented, indicating the direct involvement of the mitochondrial estrogen receptor beta (mtERβ) in the maintenance of neuronal physiology. In this study, cell lines of N2A cells stably overexpressing a mitochondrial-targeted estrogen receptor beta were generated and further analyzed to study the direct involvement of mtERβ in estrogen neuroprotective antioxidant and anti-apoptotic actions. Results from this study revealed that the presence of estrogen receptor beta in mitochondria render N2A cells more resistant to staurosporine- and H2O2-induced apoptotic stimuli, as indicated by the reduced activation of caspase-9 and -3, the increased cell viability, the increased ATP production, and the increased resistance to mitochondrial impairment in the presence or absence of 17-β estradiol (E2). Thus, the direct involvement of mtERβ in antioxidant and anti-apoptotic activities is documented, rendering mtERβ a promising therapeutic target for mitochondrial dysfunction-associated degenerative diseases.

Substrate metabolism during exercise: Sexual dimorphism and women’s specificities

ABSTRACT The aim of this review is to discuss sexual dimorphism of energy metabolism, and to describe the impact of women’s hormonal status on substrate oxidation during exercise. Many evidences indicate that sex steroids play a pivotal role in the sex-related differences of body composition and energy substrate storage. Compared with men, women rely more on fat and less on carbohydrates at the same relative exercise intensity. Scientific data suggest that 17-β oestradiol is a key hormone for the regulation of body composition and substrate metabolism. However, in women, measurements with stable isotopic tracers did not highlight any difference in whole-body substrate oxidation rates between the follicular and luteal phases of the menstrual cycle during endurance exercise. The remaining discrepancies about the effect of menstrual cycle-related hormone fluctuations on substrate oxidation could be partly explained by the exercise intensity, which is an important regulator of substrate oxidation. Due to their specific nature and concentration, the synthetic ovarian hormones contained in oral contraceptives also influence substrate metabolism during endurance exercise. However, more studies are needed to confirm that oral contraceptives increase lipolytic activity during endurance exercise without any substantial (or detectable) effect on substrate utilization. Pregnancy and menopause also modify body composition and substrate utilization during exercise through specific hormonal fluctuations. This review highlights that the hormonal status is likely to affect substrate oxidation during exercise in women emphasizing the need to take it into consideration to optimize their health and performance.

Chitosan nanoparticles alleviated endocrine disruption, oxidative damage, and genotoxicity of Bisphenol-A- intoxicated female African catfish

Bisphenol-A (BPA) is widely used in production of plastic products. It can reach the ecosystems affecting aquatic organisms most likely fishes. The purpose of this study was to study the toxic effects of BPA on the biochemical variables and oxidative stress in female African catfish, Clarias gariepinus and to estimate the protective role of chitosan nanoparticles (CSNPs) against BPA toxicity. Five groups in triplicates of fish were divided as follows: group I was control, group II was treated with CSNPs (0.66 ml/L), group III was exposed to BPA (1.43 μg/L), group IV was treated with BPA (1.43 μg/L) plus CSNPs (0.33 ml/L), and group V was treated with BPA (1.43 μg/L) plus CSNPs (0.66 ml/L) for 30 days. Blood and liver tissue samples were collected at the end of experiment for the biochemical and oxidative stress biomarkers analyses. Results exhibited that serum Follicle Stimulating Hormone (FSH) and 17-β Estradiol (E2) were significantly decreased in female catfish. While, serum Testosterone (T.) and Luteinizing Hormone (LH) were increased after exposure to BPA. Marked increment in superoxide dismutase (SOD) and malondialdehyde (MDA) levels of hepatic tissue of catfish exposed to BPA. Furthermore, significant reduction in hepatic catalase (CAT), glutathione peroxidase (GSH-px), total antioxidant capacity (TAC), reduced glutathione (GSH), and glutathione S-transferase (GST) levels were decreased significantly in BPA-exposed catfish compared to the control group. However, administration of female C. gariepinus with the low and high doses (0.33 ml/L and 0.66 ml/L) of CNPs restored the biochemical parameters to be close to the normal values of the control group and also, reduced oxidative stress induced by BPA toxicity. This improvement was evident in fish administrated with the high CSNPs dose (0.66 ml/L) compared to catfish exposed to BPA in group (III). Furthermore, the percentage of hepatic DNA damage was detected in group III exposed to BPA alone. However, it was declined after co- administration with both the low and high doses of CSNPs. The study has revealed that treatment with CSNPs has antagonistic functions against the toxicity of BPA in female African catfish.

RECEPTORS OF ENDOMETRIUM IN PREMENOPAUSAL WOMEN WITH DIFFERENT MORPHOTYPES OF ENDOMETRIAL HYPERPLASIA

Introduction. Endometrial hyperplasia is a commonproblem among premenopausal women. There are nonatypical (EH) and atypical (AH) morphotypes according tocytological atypia. Despite a mostly favorable prognosisof EH, risk of progression to atypia is nearly 2% per year.The next problem is absence of clear criteria on which casewill have an unfavorable prognosis and EH will progress toAH and endometrial cancer. Markers of response of EH andAH to the first line therapy such as progestin are not wellinvestigated either. Investigation of ER and PGR expressionin normal (NE) and hyperplastic endometrium can be usefulfor future development of treatment algorithms in differentendometrial hyperplasia morphotypes and forecastingresponses to progestin therapy.Objective: To investigate the expression of estradiol andprogesterone receptors in the glandular and stromal cells ofnormal endometrium and in the different morphotypes ofendometrial hyperplasia.Material and Methods: Endometrial samples taken from137 women were investigated: 40 – with normal proliferativeand secretory endometrium (NE), 61 – endometrialhyperplasia without atypia (ЕH), 36 – endometrialhyperplasia with atypia (AH). Routine histopathologicaland immunohistochemical (IHC) examination of nuclearantigens in the endometrium samples was conducted. Then,IHC examination was carried out on the paraffin blocksusing monoclonal and polyclonal antibodies and systems ofvisualization. Expression of estradiol (ER) and progesterone(PGR) receptors was investigated. Taking into account thatcells with positive reaction to ER and PGR have significantdifferences in the intensity of IHC coloring, we used theaverage value or H-index according to the number of cellswith positive reaction and reaction intensity. Values from0 to 50 on the H-index were considered for the absence ofER and PGR expression, from 50 to 100 - expression ofantigens to receptors was considered as weakly positive;100 points or more - as positive. Statistical processing ofresults was done using licensed program Statistics (V 6.1;Statsoft, USA).Results: ER expression of EH both in glandular cells (180±8.3) and stromal cells (170.5±4.1) was close to resultsof proliferative NE (193.1±12.2 in the glandular and 166±9.7in the stromal cells), but 1,43 times exceeded indicators inthe glandular (180±8.3 vs 125.4±5.7; p&lt;0.05) and 1.9 timesin the stromal cells (170.±4. vs 122.±4.; p&lt;0.5) of secretoryNE. PGR expression in the glandular cells of EH wasalmost the same as this indicator of NE. PGR expressionin the stromal cells of EH was 197.±9.3 points and it wassignificantly higher compared to NE. On the contrary, withAHE ER and PGR expression significantly and reliablydecreased. ER expression of glandular cells (74.6±3.9points) was 2.6 times lower compared to proliferative NE(p&lt;0.05) and 2.4 times lower to EH (р&lt;0.05). ER of stromalAHE cells dropped to 30.3±2.8, which was 5.5 times lowerthan in NE of the proliferative phase (p&lt;0.002) and 5.6times lower than in EH (p&lt;0.002). PGR expression had thesame direction and also decreased. AHE glandular PGRexpression (71.1±2.3) was 2.7-2.5 times lower than thisindicator in the proliferative and secretory NE respectively(p&lt;0.05). Reliable differences in PGR expression betweenAHE and EH were found. Glandular PGR expression indexAHE was 2.8 times lower than the same EH indicator(p&lt;0.05), stromal one was 2.4 times lower (p&lt;0.05).Conclusion: Estradiol and progesterone receptors dataof endometrium will be useful for future developmentof carcinogenesis risk stratification at the early stage,identifying patients with high risk of endometrial cancerand also for choosing the optimal way to influence thepathological process in the endometrium.

The avian central roles of alpha and beta oestrogen receptors on food intake.

In rodents, oestrogen reduces food intake centrally via alpha oestrogen receptors (αER). As there was no report about the central roles of oestrogen receptors of alpha and beta, on food intake behaviour in birds, we aimed at this subject. In the first experiment beta oestradiol, a specific beta oestrogen receptor (βER; 0, 2.5, 5,10, 15 and 31μg) was injected intracerebroventricularly (ICV) to 3-h fasted broilers. The second and third experiments were similar to the first one, but alpha oestradiol, the specific (αER; 2.5, 5 and 10μg) and MPP hydrochloride, a highly selective antagonist of (αER) (0.1, 1 and 10μg) were used. Our result showed that alpha oestradiol increased food intake and MPP hydrochloride reversed this effect. This study shows that, similar to rodents, in the avian brain (aER) are involved in food intake behavior, but despite them, their effects are stimulatory.

Hormonal Levels and Follicular Dynamics in Relation to the Oestrous Cycle in Barb and Arabian Mares, Algeria

Abstract This current study is an effort to understand the hormonal and follicular growth in the Barb and Arabian mares during the oestrous cycle; as mares are unique creatures. A total of 53 mares with 97 oestrous cycles were studied. The mares with a mean age of 10.38 ± 4.55 were examined by ultrasonography every day during their breeding season (2017). Two blood samples from each mare (n = 24) were obtained for progesterone (P4), oestrogen (oestradiol-17 beta) and follicle-stimulating hormone (FSH) determinations. The data revealed that the duration of the oestrous cycle was between 19 to 22 days. The pre-ovulatory follicle grew (3.02 ± 1.04) millimetre per day. The rate of cycles exploited in the mare (Arabian versus Barb) for conception was significantly different (P &lt; 0.001). The maximal diameter of the follicle was 50.00 millimetre. The serum progesterone levels (P &lt; 0.01) in mares were significantly higher in the luteal phase than those recorded during the time of oestrous. However, the levels of oestradiol and for FSH did not significantly change during the oestrous cycle in the mares. Determining the association between the size of the follicle and the hormone profiles were the most reliable criterion in the prediction of ovulation.

17-β Estradiol Rescued Immature Rat Brain against Glutamate-Induced Oxidative Stress and Neurodegeneration via Regulating Nrf2/HO-1 and MAP-Kinase Signaling Pathway.

Dysregulated glutamate signaling, leading to neuronal excitotoxicity and death, has been associated with neurodegenerative pathologies. 17β-estradiol (E2) is a human steroid hormone having a role in reproduction, sexual maturation, brain health and biological activities. The study aimed to explain the neuroprotective role of E2 against glutamate-induced ROS production, MAP kinase-dependent neuroinflammation, synaptic dysfunction and neurodegeneration in the cortex and hippocampus of postnatal day 7 rat brain. Biochemical and immunofluorescence analyses were applied. Our results showed that a single subcutaneous injection of glutamate (10 mg/kg) induced brain oxidative stress after 4 h by disturbing the homeostasis of glutathione (GSH) and revealed an upsurge in ROS and LPO levels and downregulated the expression of Nrf2 and HO-1 antioxidant protein. The glutamate-exposed P7 pups illustrated increased phosphorylation of stress-activated c-Jun N-terminal kinase (JNK) and p38 kinase (p38) and downregulated expression of P-Erk1/2. This was accompanied by pathological neuroinflammation as revealed by enhanced gliosis with upregulated expression of GFAP and Iba-1, and the activation of proinflammatory cytokines (TNF-α) in glutamate-injected P7 pups. Moreover, exogenous glutamate also reduced the expression of synaptic markers (PSD-95, SYP) and induced apoptotic neurodegeneration in the cortical and hippocampal regions by dysregulating the expression of Bax, Bcl-2 and caspase-3 in the developing rat brain. On the contrary, co-treatment of E2 (10 mg/kg) with glutamate significantly abrogated brain neuroinflammation, neurodegeneration and synapse loss by alleviating brain oxidative stress by upregulating the Nrf2/HO-1 antioxidant pathway and by deactivating pro-apoptotic P-JNK/P-p38 and activation of pro-survival P-Erk1/2 MAP kinase pathways. In brief, the data demonstrate the neuroprotective role of E2 against glutamate excitotoxicity-induced neurodegeneration. The study also encourages future studies investigating if E2 may be a potent neuroprotective and neurotherapeutic agent in different neurodegenerative diseases.

176-OR: STIM1 Deletion Leads to Loss of Beta-Cell Identity in High-Fat Diet-Fed Female Mice

STIM1 is an endoplasmic reticulum (ER) calcium (Ca2+) sensor that replenishes ER Ca2+ stores in a process known as store operated calcium entry (SOCE). Previously, we have shown that SOCE is impaired in the diabetic pancreatic β cell; however, the consequences of reduced β cell SOCE have not been well studied. To this end, mice with pancreatic β cell specific deletion of STIM1 (STIM1Δβ) were generated by crossing STIM1flox/flox with Ins-Cre mice and fed a high fat diet (HFD) beginning at 8 wk of age. Male STIM1Δβ mice did not show changes in glucose tolerance or body composition. In contrast, female HFD-fed STIM1Δβ mice were heavier (25.1 vs. 28.3 g, p&amp;lt;0.05), had increased fat mass (4.9 vs. 8.2g, P&amp;lt;0.01), and exhibited significant glucose intolerance (AUC IPGTT 22461 vs. 29245 mg/dL*min; p&amp;lt;0.0001) with impaired insulin secretion by in-vivo GSIS (p&amp;lt;0.05) without differences insulin tolerance, energy expenditure or food intake. Bulk RNA-sequencing of wild-type and STIM1Δβ female islets revealed reduced expression of MafA, UCN3, and Ins1 and Ins2 in STIM1Δβ islets, indicating potential loss of β cell identity. Pathway analysis showed modulation of pathways related to 17-beta estradiol (E2) signaling, with downregulation of a G-protein coupled estrogen receptor 1 (GPER), while differentially expressed genes were enriched for functions related to apoptosis, lipid metabolism, and epithelial cell differentiation. Consistently, STIM1Δβ female mice had lower β cell mass (2.984 mg vs. 1.349 mg, p&amp;lt;0.05) and higher alpha cell mass (0.1822 mg vs. 0.4463 mg, p&amp;lt;0.05). Proteomics analysis performed in STIM1-deficient INS-1 cells revealed significantly increased glucagon expression. Further, lower mobilization of intracellular cAMP levels was noted in response to treatment with E2 or G1, an agonist of GPER. These findings suggest a role for STIM1 in the maintenance of pancreatic β cell identity and indicate a potential interaction between SOCE and E2 signaling in female mice. Disclosure P. Sohn: None. P. Krishnan: None. C. Lee: None. T. Kono: None. C. Evans-molina: Advisory Panel; Self; Provention Bio, Inc., Consultant; Self; Dompe, Other Relationship; Self; Bristol-Myers Squibb Company, Nimbus Pharmaceuticals, Pfizer Inc. Funding National Institutes of Health (5T32DK064466-17, 5F30DK123996); U.S. Department of Veterans Affairs (2-I01BX001733); National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK093954-06A1); Indiana University School of Medicine; Gates Millennium Scholars Program

Electrochemical evaluation of organic pollutant estradiol in industrial effluents

Herein, this article paved a route to circumvent the tedious synthesis procedure through a facile co-precipitation technique for constructing three-dimensional (3D) microstructured cadmium molybdate (CdMoO4). The carbon nanospheres (CNS) were decorated on 3D microstructure through bath-sonication at atmospheric temperature. The uniformly disseminated and tightly pinned composite shows an excellent surface area of 45.2 m2/g, which further helps in excellent electrocatalytic properties for the electrochemical application. This superior electrocatalyst has been employed for the electrochemical oxidation of organic pollutant estradiol (ESD) for the first time towards targeting its diagnosis. Electrochemical impedance spectroscopy (EIS) substantiates the aforementioned electrocatalytic property of CdMoO4/CNS with very little charge transfer resistance (Rct). The analytical performance of CdMoO4/CNS modified screen-printed carbon electrode (SPCE) was analyzed through cyclic voltammetry and differential pulse voltammetry which demonstrates an appreciable linear range with a lower limit of detection of 3 nM and sensitivity of 2.1859 µA µM−1 cm−2. Besides, it exhibits excellent reproducibility and stability towards electrochemical detection of estradiol. Moreover, the industrial effluent analysis shows prominent recoveries in the electrochemical application and paves the way for real-time monitoring.

Sex-hormone status and emotional processing in healthy women

Fluctuations of sex hormones across the menstrual cycle allow investigating the role of 17-β estradiol and progesterone in emotional processing. We examined emotional memory, empathy-related measures, as well as mimic and skin-conductance responses to affective stimuli in 72 women either in the mid-cycle (MC-group: moderate to high estradiol, low progesterone), the later cycle (LC-group: high progesterone, moderate estradiol), or during oral contraceptive use (OC-group: low endogenous ovarian-hormone levels). In the first session, affective pictures were presented (memory encoding) while recording mimic and skin-conductance responses. Additionally, participants were exposed to a post-encoding stressor (cold pressor test). After 24 h, we tested surprise recall as well as empathy-related performance. Emotional memory was not affected by the hormone-status group, stressor, or salivary hormone levels. For the cognitive empathy-related measure, hormone status interacted with the protagonist gender. Women in the LC- and OC-groups identified emotions more accurately if depicted by female protagonists, yet the MC-group identified emotions depicted by men and women equally well. Correspondingly, the number of correctly identified emotions from male protagonists correlated positively with estradiol levels. In the affective empathy-related ratings, the OC-group showed a negativity bias, rating negative (vs. positive) emotions higher, although not associated with hormone levels. Mimic responses were not modulated by hormone-status group or related to hormone levels. Skin-conductance responses to negative pictures were heightened in the LC-group and correlated positively with progesterone levels. These data suggest a differential impact of female sex hormones on emotional processing, i.e., empathy-related performance and affective sympathetic reactivity, but not in emotional memory or affective mimic reactivity.

Relation of gilthead seabream (Sparus aurata) seasonal reproductive activity to hematology, serum biochemistry, histopathology, and Brdt gene expression.

This study aimed to find the relation of Sparus aurata (gilthead seabream) reproductive activities to some blood parameters as complete blood count, liver enzymes, some hormones related to reproduction process and microscopic findings of gonads, as well as expression of Bromodomain testis-specific gene. Eighty-eight sexually mature seabream were collected and investigated through the four seasons. Red blood cells were higher in autumn and spring. Hemoglobin was high in summer, MCV highest values ​​were seen in winter and summer, while MCHC was highest in summer. The values ​​of white blood cells increased significantly in spring, summer, and autumn compared with winter. The highest value of lymphocytes was recorded in spring and autumn. Eosinophil was recorded the highest value in the spring. The highest value of segmented neutrophils was recorded in summer. The highest value of band neutrophil was recorded in summer and winter. Alanine aminotransferase and aspartate aminotransferase showed high values in the winter. Luteinizing hormone (LH) was higher in females, males, and hermaphrodites during winter. Follicle-stimulating hormone (FSH) was higher in females during spring. The highest value of estradiol 17-β and progesterone was recorded in summer. The highest value of total testosterone was recorded in spring. Microscopically, ovaries were immature and inactive during spring and summer but well developed in autumn and winter. During spring and summer, testes were immature and began spermatogenesis process but well developed with the appearance of spermatids and spermatozoa during autumn and winter. The expression of Brdt was higher in testes than ovary. Brdt recorded high expression in autumn and spring than in summer and winter.

DEVELOPMENT AND VALIDATION OF AN HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR THE DETERMINATION OF 17-Β ESTRADIOL IN POLYMERIC NANOPARTICLES

Objective: A simple high-performace liquid chromatography method was developed and validated to determine 17-β estradiol in poly (ε-caprolactone) nanocapsules.&#x0D; Methods: The chromatographic conditions were as follows: C18 GL column with a mobile phase of acetonitrile:water (92:8 v/v) at flow rate of 1.5 mL/min with detection at 280 nm. The evaluated parameters were specificity, linearity, limits of detection and quantification, precision, accuracy, and robustness.&#x0D; Results: The method was specific and linear (r=0.9982). The limits of detection and quantification were 5.78 μg.mL-1 and 17.54 μg.mL-1, respectively. Suitable accurancy and robustness were obtained. The stability assay showed that pH variation occured after 120 days of storage, and no changes were observed regarding the size and polydispersion parameters. The applicability of the method was evaluated by determining the encapsulation efficiency of the E2 nanocapsules after 120 days of storage. The results showed values &gt;99%.&#x0D; Conclusion: The results demonstrated the applicability of the developed and validated analytical method.