Plasma Estrogen Levels Research Articles

Dietary betaine activates hepatic VTGII expression in laying hens associated with hypomethylation of GR gene promoter and enhanced GR expression

BackgroundVitellogenin (VTG) is a precursor of egg yolk proteins synthesized within the liver of oviparous vertebrates. Betaine is an important methyl donor that is reported to improve egg production of laying hens with an unclear mechanism. In the present study, we fed betaine-supplemented diet (0.5%) to laying hens for 4 wk and investigated its effect on VTGII expression in the liver.ResultsBetaine did not affect chicken weight, but significantly (P < 0.05) increased egg laying rate accompanied with a significant (P < 0.05) increase in hepatic concentration and plasma level of VTGII. Plasma estrogen level did not change, but the hepatic expression of estrogen receptor α (ERα) mRNA was significantly (P < 0.05) up-regulated. Betaine did not affect the protein content of ERα, but significantly (P < 0.05) increased hepatic expression of glucocorticoid receptor (GR) at both mRNA and protein levels. Also, ERα/GR interaction tended to be enhanced in the liver nuclear lysates of betaine-supplemented hens as determined by co-immunoprecipitation. Furthermore, dietary betaine supplementation significantly increased (P < 0.05) the hepatic expression of methyl-transfer enzymes, such as BHMT, GNMT, and DNMT1, which was associated with higher SAM/SAH ratio and hypomethylation of GR promoter regions.ConclusionsBetaine activates hepatic VTGII expression in association with modified DNA methylation of GR gene promoter, GR expression and ERα/GR interaction. Activation of hepatic VTGII expression may contribute, at least partly, to improved egg production in betaine-supplemented hens.

Disruption of Interneuron Neurogenesis in Premature Newborns and Reversal with Estrogen Treatment.

Many Preterm-born children suffer from neurobehavioral disorders. Premature birth terminates the hypoxic in utero environment and supply of maternal hormones. As the production of interneurons continues until the end of pregnancy, we hypothesized that premature birth would disrupt interneuron production and that restoration of the hypoxic milieu or estrogen treatment might reverse interneuron generation. To test these hypotheses, we compared interneuronal progenitors in the medial ganglionic eminences (MGEs), lateral ganglionic eminences (LGEs), and caudal ganglionic eminences (CGEs) between preterm-born [born on embryonic day (E) 29; examined on postnatal day (D) 3 and D7] and term-born (born on E32; examined on D0 and D4) rabbits at equivalent postconceptional ages. We found that both total and cycling Nkx2.1+, Dlx2+, and Sox2+ cells were more abundant in the MGEs of preterm rabbits at D3 compared with term rabbits at D0, but not in D7 preterm relative to D4 term pups. Total Nkx2.1+ progenitors were also more numerous in the LGEs of preterm pups at D3 compared with term rabbits at D0. Dlx2+ cells in CGEs were comparable between preterm and term pups. Simulation of hypoxia by dimethyloxalylglycine treatment did not affect the number of interneuronal progenitors. However, estrogen treatment reduced the density of total and proliferating Nkx2.1+ and Dlx2+ cells in the MGEs and enhanced Ascl1 transcription factor. Estrogen treatment also reduced Ki67, c-Myc, and phosphorylation of retinoblastoma protein, suggesting inhibition of the G1-to-S phase transition. Hence, preterm birth disrupts interneuron neurogenesis in the MGE and estrogen treatment reverses interneuron neurogenesis in preterm newborns by cell-cycle inhibition and elevation of Ascl1. We speculate that estrogen replacement might partially restore neurogenesis in human premature infants.SIGNIFICANCE STATEMENT Prematurity results in developmental delays and neurobehavioral disorders, which might be ascribed to disturbances in the development of cortical interneurons. Here, we show that preterm birth disrupts interneuron neurogenesis in the medial ganglionic eminence (MGE) and, more importantly, that estrogen treatment reverses this perturbation in the population of interneuron progenitors in the MGE. The estrogen seems to restore neurogenesis by inhibiting the cell cycle and elevating Ascl1 expression. As preterm birth causes plasma estrogen level to drop 100-fold, the estrogen replacement in preterm infants is physiological. We speculate that estrogen replacement might ameliorate disruption in production of interneurons in human premature infants.

Using three-point bending to evaluate tibia bone strength in ovariectomized young mice.

It is well known that estrogen deficiency induces a deterioration of bone strength in aged females. The aim of this study is to determine the effect of estrogen depletion on tibia bone strength in sexually mature mice that are still undergoing skeletal maturation. At 8weeks of age, C57BL/6 female mice underwent an ovariectomy (OVX) or sham (SHAM) surgery. Mice were killed at 2, 4, or 8weeks post-surgery. Tibia length and cross-sectional area continued to increase in both treatment groups until 4weeks post-surgery. Compared to SHAM mice, OVX mice demonstrated a significant reduction in uterine weight and plasma estrogen levels. Three-point bending was used to quantify the mechanical properties (breaking point, stress, stiffness, and elasticity) of the tibia. The tibias from the SHAM mice had a higher breaking point than all the age-matched OVX mice. At 8weeks post-surgery, the tibias from the SHAM mice demonstrated higher elasticity, stress, and stiffness than the younger SHAM mice and the age-matched OVX mice. Compared to the SHAM mice, our study suggests that (1) there is a reduction in the mechanical strength of tibias from young OVX mice, and (2) the greatest decline in tibia strength of the OVX mice was once they reached skeletal maturity.

A role of alpha-tocopherol and phylloquinone in the modulation of uterine contractility and reproductive function in mouse models

Background and aimAlpha-tocopherol has been implicated in reproduction processes, and deficiency of phylloquinone has been associated with serious complications in pregnancy. This study was therefore aimed at investigating the effects of phylloquinone and alpha-tocopherol on uterine contractility and female reproductive function using mouse models. Materials and methodsBoth in vivo and ex vivo animal models were employed and designed to assess changes on uterine contractility and reproductive functions in the non-pregnant uterus. The effect of alpha-tocopherol and phylloquinone on spontaneous uterine contractions, oxytocin-induced uterine contractions (11.82nM) and high KCl-induced tonic uterine contractions (80mM) were assessed. The effect of subcutaneous administration of alpha-tocopherol (10mg/kg) on reproductive hormone levels and reproductive tissues were also determined. ResultsAlpha-tocopherol increased the force of contractions while phylloquinone decreased the force of uterine contractions. Plasma levels of luteinizing hormone (P<0.01), estrogen (P<0.01) and progesterone (P<0.001) were elevated in the presence of alpha-tocopherol after 6 days subcutaneous administration. ConclusionsAlpha-tocopherol and phylloquinone have been shown to directly modulate uterine contractility and reproductive function and may contribute to the management and treatment of reproductive disorders.

Haemorheological changes associated with the menstrual cycle and oral contraceptive therapy

In this study of 3 normal females and 30 receiving oral contraceptives (OCs) no association was established between plasma viscosity whole blood viscosity (WBV) corrected for a 45% packed cell volume red cell filterability and levels of plasma estrogen and progesterone. In OC users there was a transient rise in both plasma and WBV recorded after 1 month with reversal by 3 months and stabilization thereafter. (authors)

The interaction of estrogen and CSE/H2S pathway in the development of atherosclerosis.

Both estrogen and hydrogen sulfide (H2S) have been shown to inhibit the development of atherosclerosis. We previously reported that cystathionine γ-lyase knockout (CSE-KO) male mice develop atherosclerosis earlier than male wild-type (WT) mice. The present study investigated the interaction of CSE/H2S pathway and estrogen on the development of atherosclerosis in female mice. Plasma estrogen levels were significantly lower in female CSE-KO mice than in female WT mice. NaHS treatment had no effect on plasma estrogen levels in both WT and CSE-KO female mice. After CSE-KO and WT female mice were fed with atherogenic diet for 12 wk, plasma lipid levels were significantly increased and triglyceride levels decreased compared with those of control diet-fed mice. Atherogenic diet induced more atherosclerotic lesion, oxidative stress, intracellular adhesion molecule-1 (ICAM-1), and NF-κB in CSE-KO mice than in WT mice. Estrogen treatment of atherogenic diet-fed WT mice attenuated hypercholesterolemia, oxidative stress, ICAM-1 expression, and NF-κB in WT mice but not in atherogenic diet-fed CSE-KO mice. Furthermore, H2S production in both the liver and vascular tissues was enhanced by estrogen in WT mice but not in CSE-KO mice. It is concluded that the antiatherosclerotic effect of estrogen is mediated by CSE-generated H2S. This study provides new insights into the interaction of H2S and estrogen signaling pathways on the regulation of cardiovascular functions.NEW & NOTEWORTHY Female cystathionine γ-lyase (CSE)-knockout mice have significantly lower plasma estrogen levels and more severe early atherosclerotic lesion than female wild-type mice. H2S production in liver and vascular tissues is enhanced by estrogen via its stimulatory effect on CSE activity. The antiatherosclerotic effect of estrogen is mediated by CSE-generated H2S.

Lacking of estradiol reduces insulin exocytosis from pancreatic β-cells and increases hepatic insulin degradation

Low levels of plasma estrogens are associated with weight-gain, android fat distribution, and a high prevalence of obesity-related comorbidities such as glucose intolerance and type II diabetes. The mechanisms underlying the association between low levels of estrogens and impaired glucose homeostasis are not completely understood. To begin to test this, we used three-month-old female C57BL/6J mice that either underwent ovariectomy (OVX) or received a sham surgery (Sham), and we characterized glucose homeostasis. In a subsequent series of experiments, OVX mice received estradiol treatment (OVX+E2) or vehicle (OVX) for 6 consecutive days. As has been previously reported, lack of ovarian hormones resulted in dysregulated glucose homeostasis. To begin to explore the mechanisms by which this occurs, we characterized the impact of estrogens on insulin secretion and degradation in these mice. Insulin secretion and plasma insulin levels were lower in OVX mice. OVX mice had lower levels of pancreatic Syntaxin 1-A (Synt-1A) protein, which is involved in insulin extrusion from the pancreas. In the liver, OVX mice had higher levels of insulin-degrading enzyme (IDE) and this was associated with higher insulin clearance. Estradiol treatment improved glucose intolerance in OVX mice and restored insulin secretion, as well as normalized the protein content of pancreatic Synt-1A. The addition of estrogens to OVX mice reduced IDE protein to that of Sham mice. Our data suggest loss of ovarian estradiol following OVX led to impaired glucose homeostasis due to pancreatic β-cell dysfunction in the exocytosis of insulin, and upregulation of hepatic IDE protein content resulting in lower insulinemia, which was normalized by estradiol replacement.

Hemorheological effects of secoisolariciresinol in ovariectomized rats.

Postmenopausal women often develop hemorheological disorders which may affect the systemic blood circulation and present a cardiovascular risk factor. We evaluated effects of secoisolariciresinol (SECO), a phytoestrogen, on hemorheological parameters and lipid peroxidation in a model of the age-related and/or surgical menopause induced by ovariectomy in rats. Arterial blood was sampled from sham-operated female rats, ovariectomized rats (OVX), and OVX treated with SECO (OVXSECO) (20 mg/kg/day intragastrically for two weeks). Plasma estrogen concentration and the following hemorheological parameters were measured: RBC aggregation (half-time of aggregation, T1/2; amplitude of aggregation, AMP; aggregation index, AI), RBC deformability (elongation index, EI), whole blood viscosity at the shear rate of 3-300s-1, plasma viscosity, hematocrit, plasma fibrinogen. Lipid peroxidation was evaluated by measuring conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS) in plasma. Ovariectomy in rats caused a 60% decrease in plasma estrogen level and triggered the development of macro- and microhemorheological abnormalities. Blood viscosity increased by 12-31%, RBC elongation index reduced by 16-28%, and T1/2 and AI increased by 35% and 29% respectively. The increase in blood viscosity correlated predominantly with reduced RBC deformability. Plasma CD and TBARS were elevated by 47% and 104% respectively. SECO therapy for OVX rats reduced blood viscosity by 9-18% and T1/2 by 32%, and increased EI by 4-17%. SECO therapy disrupted the correlation between blood viscosity and RBC deformability. Lipid peroxidation was significantly inhibited, as shown by the reduction in CD and TBARS plasma concentrations by 89% and 70% respectively. SECO did not affect plasma viscosity, estrogen or fibrinogen levels. SECO treatment for OVX rats improves blood macro- and microrheological parameters, possibly through antioxidant protection of RBC.

Combination of Melatonin and Metformin Hydrochloride for Treatment Polycystic Ovarian in Female Rats

Background: Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder, results in menstrual abnormalities, androgynism and infertility. In the case of women or others animals with PCOS wishing to treat infertility with the aim of becoming pregnant, the most commonly used is metformin hydrochloride. Recent studies have analyzed the combination of metformin hydrochloride with melatonin in oncological treatment but not to treatment of polycystic ovary syndrome (PCOS). The aim of the present study was to analyze the effectiveness of the combination of metformin hydrochloride and melatonin in the treatment of PCOS to improve the fertility of rats and your hormonal alterations.Materials, Methods &amp; Results: This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Federal Rural of Pernambuco (Permit Number: 23081.009130/2010). A total of 50 albino Wistar rats were used. The animal laboratory of an academic research environment, were randomly separated into five groups consisting of 10 females each. After inducing PCOS, the rats were treated with metformin hydrochloride, and/or melatonin, and the results compared with standard and ultrasound confirmed. The physiological similarities were confirmed by our academic researchers morphological science, and published to the association results of effects syndrome induction through constant lighting in reputable magazine recently. This article was analyzed histological of the implantation sites and ovaries, and the estradiol and progesterone levels on the seventh day of gestation, and the other rats for monitoring pregnancy and morphological identification of possible fetal abnormalities, weight measurement and quantification of offspring. The rats were anaesthetized with intraperitoneal injections of ketamine hydrochloride (80 mg/kg) and xylazine (6 mg/kg) to allow analysis of the reproductive organs. Main outcome measures: The study included histopathology, histochemical and quantitative (of the implantation sites) tests, ultrasound analysis, weight benchmarking and ovarian histology tests, as well as comparison of serum estradiol and progesterone levels, and the morphological assessment of offspring. Results paper shows pharmacological treatment reduced the time needed for pregnancy, increased the plasma progesterone levels, the number and weight of offspring, and reduced plasma estrogen levels and collagen fiber grade, improving blastocyst-endometrium interaction and fetal development.Discussion: Our team of researchers confirmed in a previous paper; in addition, the main experimental model used in research about PCOS in recent years, and considered appropriate combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the POS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring. The treatment with a combination of metformin hydrochloride and melatonin was more effective against hormonal alterations produced by PCOS, allowing a normalization of biochemical parameters during pregnancy, than monotherapeutic treatment with these drugs. In conclusion, proposed drug combination is a viable option to treatment of polycystic ovary syndrome and improved fetal development. This article allows suggest that further research should be conducted to examine effects associated with these drugs in the treatment of diseases of the female reproductive system experimentally. Only such treatment later in animals and humans suggest.

Long-term exposure to electromagnetic radiation from mobile phones and Wi-Fi devices decreases plasma prolactin, progesterone, and estrogen levels but increases uterine oxidative stress in pregnant rats and their offspring.

TRPV1 cation channels are the possible molecular pathways responsible for changes in the hormone, oxidative stress, and body temperature levels in the uterus of maternal rats following a year-long exposure to electromagnetic radiation exposure from mobile phones and Wi-Fi devices. It is likely that TRPV1-mediated Ca(2+) entry in the uterus of pregnant rats involves accumulation of oxidative stress and opening of mitochondrial membrane pores that consequently leads to mitochondrial dysfunction, substantial swelling of the mitochondria with rupture of the outer membrane and release of oxidants such as superoxide (O2 (-)) and hydrogen peroxide (H2O2). The superoxide radical is converted to H2O2 by superoxide dismutase (SOD) enzyme. Glutathione peroxidase (GSH-Px) is an important antioxidant enzyme for removing lipid hydroperoxides and hydrogen peroxide and it catalyzes the reduction of H2O2 to water.

Role of sex steroids and their receptors in human preterm infants: Impacts on future treatment strategies for cerebral development

Preterm birth is a major risk factor for cerebral complications, such as hemorrhage or periventricular leukomalacia, which lead to lifelong neurodevelopmental deficits. Hypoxia/ischemia, inflammation, hyperoxia, and prematurity itself contribute to the extent of impaired neurodevelopment. Preterm birth leads to disruption of the placental supply of estrogens and progesterone. Postnatally, the plasma levels of estrogens and progesterone drop 100-fold. Preterm infants are deprived of the placental supply of these hormones for up to sixteen weeks. Thus, supplementation of estradiol and progesterone to mimic intrauterine conditions may potentially improve a premature infant́s extrauterine development and help protect the brain against neurological complications. However, preliminary clinical studies did not find improved outcomes except for a trend towards less cerebral palsy. The decrease in estrogen and progesterone concentrations is accompanied by persistent, high postnatal production of fetal zone steroids, mainly dehydroepiandrosterone, which serve as precursors for maternal estrogen synthesis during pregnancy. This commentary will combine knowledge from endocrinology, pharmacology, and neonatology to explain the discrepancies between promising animal models and clinical findings. Most important targets will be classical and non-classical estrogen receptors, which interact differently—not only with estrogens but also with fetal zone steroids. The fetal zone is unique among humans and higher primates. Therefore, a clearly defined model is required to study the role of sex steroids and their receptors before further clinical studies begin.

Abstract 5038: Role of the short isoform of the progesterone receptor in hormone-regulated invasiveness of breast cancer cells at pre- and post-menopausal levels of estrogen and progesterone

Abstract Introduction: High expression of the progesterone receptor (PR) isoform A, relative to PR isoform B, is clinically associated with progression to invasiveness in estrogen receptor (ER)-positive breast cancer and lower disease free survival. This is apparently at odds with in vitro studies implicating PR-B in mediating progestin-induced invasiveness. As the in vitro studies were conducted in the absence of estrogen (E2) signaling, we considered the possibility that modulation of E2 action may comprise a distinct aspect of the regulation of invasiveness by progestins. Methods: Standard ER+/PR+ and ER+/PR+/HER2+ breast cancer cell line models were studied, as well as recombinant cells expressing a single PR isoform. For the progestin hyper-sensitization studies, PR-A was over-expressed by lentiviral infection. Hormonal influence on invasiveness was studied using the Boyden chamber assay. Gene expression was examined by Illumina DNA microarray analysis and by Taq-Man real time RT-PCR assays. Results: E2 strongly suppressed invasiveness of ER+ breast cancer cells at concentrations below 0.01nM. At low (&amp;lt; 1 nM) concentrations, progesterone, R5020 and medroxyprogesterone acetate completely abrogated the inhibition of invasiveness by E2. It was only in a higher (5nM - 50 nM) concentration range that progestins induced invasiveness in the absence of E2. The ability of progestins to rescue invasiveness from E2 regulation was exclusively mediated by PR-A whereas PR-B mediated the E2-independent component of progestin-induced invasiveness. Overexpression of PR-A in PR-A+/PR-B+ cells lowered the progestin concentration needed to completely rescue invasiveness (to &amp;lt; 0.2 nM). Progesterone opposed E2 regulation of a distinctive set of genes, exclusively through PR-A. Conclusion: At relatively low concentrations, progesterone influences breast cancer cell invasiveness by rescuing it from E2 regulation via PR-A, whereas at higher concentrations the hormone also induces invasiveness independent of E2 signaling, through PR-B. The findings establish a direct functional link between PR-A and progression of luminal breast cancer in the context of the entire range of pre- and post-menopausal plasma and breast tissue estrogen and progesterone levels. Citation Format: Thomas B. McFall, Mugdha Patki, Rayna Rosati, Manohar Ratnam. Role of the short isoform of the progesterone receptor in hormone-regulated invasiveness of breast cancer cells at pre- and post-menopausal levels of estrogen and progesterone. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5038. doi:10.1158/1538-7445.AM2015-5038

Spontaneous failure of the estrous cycle induces anxiogenic-related behaviors in middle-aged female mice

Clinical studies have shown that women during perimenopause and menopause have a higher incidence in the diagnoses of psychiatric problems compared with men. However, little literature information about the influence of spontaneous perimenopause on anxiety- and mood-related behaviors in mice is available. To this aim, we compared the behavioral responses of middle-aged and young adult female mice both in the diestrus phase in the elevated plus-maze, open field and forced swimming tests. In middle-aged mice, the duration of the estrous cycle was significantly prolonged compared to young adults, thus indicating that our middle-aged mice are in the perimenopausal period. In the elevated plus-maze test, middle-aged mice explored less the open arms when compared to young adults, suggesting an anxiogenic-like phenotype. No significant differences were observed in the estrogen plasma levels and emotional behavior in the forced swim and open field tests. In conclusion, the spontaneous failure of the estrous cycle increased anxiety in middle-aged females. These data suggest that the perimenopausal period has a significant influence on anxiety-related behaviors in female mice.

IMPACTO CLÍNICO DE ESTROGENOTERAPIA RESIDUAL EN POSMENOPÁUSICAS

Objetivos: a) Determinar la concentración plasmática residual de estrógeno después de siete días de culminada su administración en la mujer posmenopáusica. b) Precisar si hay diferencia de concentración plasmática según administración oral (0, 625mg de estrógenos conjugados) o transdérmica (50 mg 17 beta estradiol). c) Estudiar el impacto clínico de la concentración plasmática residual con el índice Posmenopáusico de Blatt Kupperman (IMBK) MATERIAL Y MÉTODOS: Se efectuó dosaje de concentración plasmática de estrógenos pretratamiento y a los 7 días postratamiento de dos y cuatro meses, usando vía oral y transdérmica; se evaluó sintomatología en esos tres momentos con el IMBK. RESULTADOS: La concentración plasmática de estrógenos, a siete días de concluida la estrogenoterapia, se mantiene por encima de la basal, luego de dos y cuatro meses de tratamiento. El IMBK disminuye en 70%, independiente de la concentración plasmática residual de estrógenos y de la vía de administración. CONCLUSIONES . La concentración plasmática de estrógenos se mantiene por encima de la basal a 7 días de culminada la estrogenoterapia, siendo mayor cuando se usa vía transdérmica, con notable mejoría según IMBK, independientemente de la vía de administración y concentración plasmáitica de estrógenos.

Influence of melatonin on plasma glucose-regulated protein 78 levels in ovariectomized female rats

In rats with surgically induced primary ovarian failure, melatonin may influence intra-retroperitoneal fat and a number of metabolic factors, which are risk factors for a number of disorders, including endometrial cancer (EC). The aim of this study is to investigate the influence of melatonin treatment in female rats with surgically induced menopause on the plasma glucose-regulated protein ​​78 (GRP78) levels as a risk factor of EC. In the current study 40 mice were included. At 14 days post-ovariectomy the animals were exposed to estrogen replacement treatment and combined treatment of estrogen and melatonin. The treatment duration, with products and doses recommended for veterinary use, was 12 consecutive weeks. The plasma estrogen and GRP78 level was measured. Groups which received estrogen associated with melatonin had a lower level of GRP78 compared to the control group. This study supports the idea that melatonin influences plasma estrogen level, which is directly, correlated with plasma GRP78 level, suggesting the implication of GRP78 in the pathogenesis of EC.

The Serum Level of Estrogen and Progesterone and Their Ratio in Patients with Ischemic Stroke: A Comparative Study

Article type: Original Article Background: The role of estrogen and progesterone in stroke is suggested in previous studies, but yet is controversial. Objectives: Comparing the plasma levels of estrogen and progesterone and their ratio in ischemic stroke patients and healthy population. Materials and Methods: This cross-sectional comparative study was conducted from March to September of 2013. Sixty-six female patients older than 60 years with ischemic stroke who referred within the first 12 hour of their neurologic symptoms were included. A total of 48 women who were in the same age range comprised the control group. The serum levels of progesterone and 17-β-estradiol concentrations were measured. The data were analysed by Chi 2 test, univariate and logistic regression models in SPSS software 19. Results: There was no significant difference between case and control groups in serum levels of estrogen (28.66 ± 13.60 vs. 35.72 ± 28.36) and progesterone (1.07 ± 0.83 vs. 1.40 ± 1.87) and their ratio (p > 0.05). But in multivariate analysis, estrogen (p = 0.033), progesterone (p = 0.02) and the interaction between them (p = 0.013) remained as associated factors. In addition, the higher ratio of estrogen to progesterone indicates the less ability of patients, which one unit increase in this ratio results in 0.072 reduction in NIHSS (National Institutes of Health Stroke Scale) score. Conclusions: The level of estrogen and progesterone and interaction between them are associated with ischemic stroke. The ratio of estrogen to progesterone has reverse association with score of the ability of patient according to NIHSS.

Glucocorticoid-induced impairment of long-term memory retrieval in female rats: Influences of estrous cycle and estrogen

Using an inhibitory avoidance (IA) task, the effects of glucocorticoids on memory retrieval in intact and ovariectomized (OVX) female rats were investigated. Young adult female rats were trained in a one trial IA task (1-mA, 3-s footshock). The latency to reenter the dark compartment of the apparatus was recorded in the retention test performed 48h after training. Pre-retrieval injection of corticosterone (CORT, 1, 3, and 10mg/kg) to OVX rats impaired memory retrieval at all doses tested. Similar administration of CORT (3mg/kg) in intact female rats impaired memory retrieval in the estrus phase (when endogenous plasma levels of estrogen are low) but not in the proestrus phase (when endogenous levels of estrogen are high). Concurrent administration of CORT (3mg/kg) and 17-β-estradiol (15μg/kg) in both proestrus and estrous phases impaired memory retrieval. Our findings indicate that the effects of corticosterone on memory retrieval are modulated by the estrous cycle and 17-β-estradiol.

Caloric Restriction Promotes the Reserve of Follicle Pool in Adult Female Rats by Inhibiting the Activation of Mammalian Target of Rapamycin Signaling

Caloric restriction (CR) is known to increase the number of primordial follicles and prolong the reproductive life span. However, how CR modulates follicular development is not well understood. In the present study, we examined the effects of CR on follicular development in rats and investigated the underlying mechanism. After 10 weeks of CR or high-fat diet, ovarian follicles at different developmental stages were examined by histological analysis. Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrogen (ESG) were measured, and the levels of mammalian target of rapamycin (mTOR), p70S6 kinase (p70S6K), and phosphorylated p70S6K in the ovary were detected by Western blot. The results showed that the reserve of follicle pool in CR rats was increased, accompanied by decreased level of phosphorylated p70S6K in the ovary, and decreased serum LH, FSH, and ESG levels. Taken together, these results suggest that CR may suppress ovarian follicular development and enhance the follicle pool reserve by inhibiting mTOR signaling.

Analogs of Luteinizing Hormone-Releasing Hormone in the Treatment of Endometriosis

Agonists of luteinizing hormone-releasing hormone (LHRH) induce a reversible hypoestrogenic state through the down-regulation of LHRH receptors and desensitization of the pituitary. Since endometrial implants are estrogen sensitive, LHRH agonists have frequently been used for medical treatment of endometriosis. Nowadays, LHRH agonists can be considered in general as a second-line medical treatment for endometriosis-related symptoms, as oral therapy with dienogest is as effective and has fewer side effects. However, therapy with LHRH agonists for 3-6 months prior to in vitro fertilization remains the treatment of choice in patients with endometriosis, as it significantly increases pregnancy rates. LHRH agonists are used prior to surgery and as an adjuvant after an operation to prevent recurrence or prolong disease-free intervals. Adverse effects of LHRH agonists are due to hypoestrogenism and include hot flushes, vaginal dryness, loss of libido, sleep disturbances and a diminished bone density which limits the duration of their administration to 6 months. For long-term treatment, add-back of estrogen and/or progestin,/or progestin only with or without bisphosphonates, can be used, but existing studies only cover a 12-month period of treatment. LHRH antagonists competitively block the pituitary receptors for LHRH. Consequently, a partial pharmacological hypophysectomy with a reduction of the estrogen levels to a desired level is possible if LHRH antagonists are adequately dosed. As endometriotic implants require relatively high levels of estrogen, partially lower plasma levels of estrogens are sufficient to prevent the loss of bone density. A long-term treatment without add-back therapy is also possible.

Effects of estrogen on glutathione and catalase levels in human erythrocyte during menstrual cycle.

The present study evaluated the effects of physiological serum estrogen during the menstrual cycle on glutathione (GSH) and catalase activities. The sample included 43 healthy females between the ages of 22 and 51 years. The subjects were divided into two groups according to the stage of the menstrual cycle. Group A consisted of 16 samples extracted between days 10 and 20 from the first day of menstruation when estrogen levels were considered to be at their highest. Group B consisted of 27 samples extracted during other times of the estimated 30 days of menstruation. Data showed that the estrogen level in group A (184±106 pg/ml) was higher than that in group B (105±56 pg/ml) (P<0.01). The GSH and catalase levels in group A (4.4±2.3 µg/mg and 210±72 IU/mg, respectively) were also significantly higher compared to the levels in group B (3.2±1.8 µg/mg and 168±62 IU/mg, respectively) (P <0.05). Spearman's rank correlation showed that the expression of catalase in red blood cells significantly correlated with serum estrogen level but not with GSH. However, the changes in estrogen plasma levels, erythrocyte GSH level and catalase activity suggested that the consumption of GSH and catalase in erythrocyte during the menstrual cycle may be associated with the level of estrogen present in the bloodstream.