Existence Of Estrogen Receptors Research Articles

The Uncoupling Effect of 17β-Estradiol Underlies the Resilience of Female-Derived Mitochondria to Damage after Experimental TBI.

Current literature finds females have improved outcomes over their male counterparts after severe traumatic brain injury (TBI), while the opposite seems to be true for mild TBI. This begs the question as to what may be driving these sex differences after TBI. Estrogen is thought to be neuroprotective in certain diseases, and its actions have been shown to influence mitochondrial function. Mitochondrial impairment is a major hallmark of TBI, and interestingly, this dysfunction has been shown to be more severe in males than females after brain injury. This suggests estrogen could be playing a role in promoting "mitoprotection" following TBI. Despite the existence of estrogen receptors in mitochondria, few studies have examined the direct role of estrogen on mitochondrial function, and no studies have explored this after TBI. We hypothesized ex vivo treatment of isolated mitochondria with 17β-estradiol (E2) would improve mitochondrial function after experimental TBI in mice. Total mitochondria from the ipsilateral (injured) and contralateral (control) cortices of male and female mice were isolated 24 h post-controlled severe cortical impact (CCI) and treated with vehicle, 2 nM E2, or 20 nM E2 immediately before measuring reactive oxygen species (ROS) production, bioenergetics, electron transport chain complex (ETC) activities, and β-oxidation of palmitoyl carnitine. Protein expression of oxidative phosphorylation (OXPHOS) complexes was also measured in these mitochondrial samples to determine whether this influenced functional outcomes with respect to sex or injury. While mitochondrial ROS production was affected by CCI in both sexes, there were other sex-specific patterns of mitochondrial injury 24 h following severe CCI. For instance, mitochondria from males were more susceptible to CCI-induced injury with respect to bioenergetics and ETC complex activities, whereas mitochondria from females showed only Complex II impairment and reduced β-oxidation after injury. Neither concentration of E2 influenced ETC complex activities themselves, but 20 nM E2 appeared to uncouple mitochondria isolated from the contralateral cortex in both sexes, as well as the injured ipsilateral cortex of females. These studies highlight the significance of measuring mitochondrial dysfunction in both sexes after TBI and also shed light on another potential neuroprotective mechanism in which E2 may attenuate mitochondrial dysfunction after TBI in vivo.

Benign Paroxysmal Positional Vertigo Risk Factors Unique to Perimenopausal Women.

Many investigations have found common occurrences of benign paroxysmal positional vertigo (BPPV) in women, and clinical experience has shown that BPPV can develop due to increased hormonal fluctuations, especially during menopause. Therefore, knowledge about neurochemicals and their involvement with BPPV is imperative for the management of neurological issues in women. This review will discuss appropriate gender-based considerations of BPPV based on experimental and clinical evidence. The studies describe 2 lines of evidence regarding the association of perimenopause in women and the development of BPPV: (1) experimental evidence: the existence of estrogen receptors in the inner ear, otoconial malformations in osteopenic/osteoporotic rats, changes in otoconin 90 caused by hormone replacement therapy, and impaired calcium absorption following estrogen deprivation corrected by estrogen replacement therapy and (2) clinical evidence: epidemiological aspects, osteoporosis and estrogen deficiency. Future studies are necessary to validate the effects of hormonal replacement therapy and phytoestrogen in women with recurrent BPPV.

Fitting Cure Rate Model to Breast Cancer Data of Cancer Research Center.

The Cox PH model is one of the most significant statistical models in studying survival of patients. But, in the case of patients with long-term survival, it may not be the most appropriate. In such cases, a cure rate model seems more suitable. The purpose of this study was to determine clinical factors associated with cure rate of patients with breast cancer. In order to find factors affecting cure rate (response), a non-mixed cure rate model with negative binomial distribution for latent variable was used. Variables selected were recurrence cancer, status for HER2, estrogen receptor (ER) and progesterone receptor (PR), size of tumor, grade of cancer, stage of cancer, type of surgery, age at the diagnosis time and number of removed positive lymph nodes. All analyses were performed using PROC MCMC processes in the SAS 9.2 program. The mean (SD) age of patients was equal to 48.9 (11.1) months. For these patients, 1, 5 and 10-year survival rates were 95, 79 and 50 percent respectively. All of the mentioned variables were effective in cure fraction. Kaplan-Meier curve showed cure model's use competence. Unlike other variables, existence of ER and PR positivity will increase probability of cure in patients. In the present study, Weibull distribution was used for the purpose of analysing survival times. Model fitness with other distributions such as log-N and log-logistic and other distributions for latent variable is recommended.

Possible direct induction by estrogen of calcitonin secretion from ultimobranchial cells in the goldfish

The plasma level of calcitonin (CT), a calcium (Ca)-regulating hormone, is known to increase in female teleosts during the reproductive period. In the present study, a correlation between plasma CT and Ca and one between plasma CT and the gonad somatic index were demonstrated in the female goldfish but not in the male. To clarify the relationship between CT and Ca, we examined the plasma CT and Ca levels after injecting immature goldfish with estrogen. At day 1, the plasma CT level significantly increased, whereas the plasma Ca level was not changed from its initial level. This result suggests that the trigger of CT secretion is estrogen and that estrogen directly acts on the ultimobranchial gland (UBG), a CT-secreting organ. To determine whether the UBG is equipped with estrogen receptor (ER), an ER binding assay and immunohistochemical staining of UBG cells with an antibody against ER were conducted. As a result, estrogen-specific binding ( K d, 18.52 nM; B max, 1.35 pmol/mg protein) and ER-immunoreactivity in the UBG were demonstrated. Furthermore, the expression of α,β, and γ types of ER in the UBG was also detected by use of the reverse-transcription polymerase chain reaction. Thus, we concluded that estrogen acts on the UBG to induce the release of CT, which in turn plays an important role in reproduction directly and/or indirectly through Ca. This is the first report on the existence of ERs in a teleost UBG and the occurrence of CT secretion caused by estrogen.

Comparison of in vivo and in vitro subcellular localization of estrogen receptors α and β in oligodendrocytes

The existence of estrogen receptors (ERs) in oligodendrocytes (OLGs) in vivo and in vitro is unresolved, as their presence has been reported in some studies and their absence in others. Using molecular and immunocytochemical techniques, we describe the subcellular localization of ERalpha and ERbeta in OLGs in vivo and in vitro. Both ERalpha and ERbeta are detected in an immortalized OLG cell line and in enriched OLG cultures by RT-PCR and western blot. Immunocytochemistry of OLGs from enriched cultures shows ERalpha receptors are nuclear, whereas ERbeta receptors are cytoplasmic. Confocal and deconvolution microscopy of enriched OLG cultures reveals ERbeta immunoreactivity is concentrated in perikarya and veins of OLG membrane sheets; lesser reactivity is present in their plasma membranes and nuclei. In vivo, we readily detect ERalpha in neurons but not in OLGs, even though we used different fixation procedures and different ERalpha antibodies. The presence of ERalpha in cultured OLGs may be due to culture media that contains factors stimulating ERalpha expression but are reduced in normal brain. In vivo, ERbeta immunoreactivity is readily detectable in OLG cytoplasm and in myelin sheaths. Incubation of glial cultures without or with increasing concentrations of 17beta-estradiol (E2) shows that E2 significantly accelerates OLG process formation.

The effect of oxidative stress on ERα and ERβ expression

The formation of intracellular reactive oxygen and nitrogen species (ROS and RNS) has been implicated in the pathogenesis of a variety of diseases. In excess, ROS and their byproducts may cause oxidative damage and be cytotoxic to cells. Recently, it has been established that these oxidants can also act as subcellular messengers in gene regulatory and signal transduction pathways. Estrogen, on the other hand, is known to offer protection from coronary artery diseases in post-menopausal women and to be involved in various ROS-related diseases, such as Alzheimer’s and Parkinson’s diseases, diabetes and aging. The existence of estrogen receptors in these tissues lead us to investigate whether ROS can regulate their expression. We demonstrated here, for the first time, that oxidative stress induced by hydrogen peroxide (H 2O 2), Fe 2+, 2,2′-azobis(2-amidinopropane)dihydrochloride (AAPH) and activated macrophages, affect the expression of estrogen receptors α and β (ERα and ERβ) differently, demonstrating cell-specific response which can be blocked by antioxidants. This data suggest that oxidative stress and the production of ROS/RNS function as physiological regulators of ERα and ERβ expression. This may provide a new insight into the ERβ-dependent protective action of estrogen and phytoestrogens in inflammation involving diseases, and may contribute to the development of novel therapeutic treatment strategies.

CNS location of uterine-related neurons revealed by trans-synaptic tracing with pseudorabies virus and their relation to estrogen receptor-immunoreactive neurons

Retrograde, transneuronal tracing with Bartha's strain of pseudorabies virus was used in rats to identify spinal cord, brainstem and hypothalamic loci of uterine-related neurons that could function in the regulation of uterine activity. Based on the premise that estrogen might influence such uterine-related neurons, the existence of estrogen receptors in neurons in these same loci was examined. Viral injections were made into the uterine cervix, body and cervical end of the uterine horns, and the rats allowed to survive for four to six days. After four days, mainly the spinal cord, medulla and pons contained virus-infected neurons. After longer survival times, progressively higher levels of the neuraxis contained viral-labeled neurons, so that by six days hypothalamic uterine-related neurons were identified. First-order virus-infected neurons were visualized by immunohistochemistry in the pelvic paracervical parasympathetic ganglia and in inferior mesenteric sympathetic ganglia. Preganglionic and putative interneurons were labeled in the lumbosacral spinal cord and thoracic spinal cord mainly in the lateral horn area (sacral parasympathetic nucleus and intermediolateral nucleus), lateral aspect of the dorsal horn, intermediate gray, lamina X and dorsal gray commissural area. In the brainstem, labeling was most evident and consistent in the nucleus tractus solitarius, ventrolateral medulla, raphe magnus and pallidus nuclei, parapyramidal area, A5 cell group, Barrington's nucleus of the pons and periaqueductal gray of the midbrain. In the hypothalamus, virus-infected neurons were most marked in the paraventricular nucleus, with fewer in the medial preoptic area and ventromedial hypothalamic nucleus. Estrogen receptor-immunoreactive neurons were most often present among the virus-labeled uterine-related neurons of the spinal cord, nucleus tractus solitarius, ventrolateral medulla, periaqueductal gray, medial preoptic area and ventromedial hypothalamic nucleus. These results identify a multisynaptic pathway of neurons whose eventual output is involved in uterine functions, whose distribution is similar to that revealed by pseudorabies virus tracing from other visceral organs, and which are often mixed among estrogen-responsive neurons.

Estrophilin immunoreactivity versus estrogen receptor binding activity in meningiomas: Evidence for multiple estrogen binding sites

The existence of estrogen receptors in human meningiomas has long been a controversial issue. This may be explained, in part, by apparent heterogeneity of estrogen binding sites in meningioma tissue. In this study, estrogen receptors were determined in 58 meningiomas with an enzyme immunoassay using monoclonal antibodies against human estrogen receptor protein (estrophilin) and with a sensitive radioligand binding assay using 25 1-labeled estradiol 5 I-estradiol) as radioligand. Low levels of estrophilin immunoreactivity were found in tumors from 62% of patients, whereas radioligand binding activity was demonstrated in about 46% of the meningiomas examined. In eight (14%) tissue samples multiple binding sites for estradiol were observed. The immunoreactive binding sites correspond to the classical, high affinity estrogen receptors: the K d for 25 I-estradiol binding to the receptor was approximately 0.2 nM and the binding was specific for estrogens. The second, low affinity class of binding sites considerably influenced measurement of the classical receptor even at low ligand concentrations. The epidemiological and clinical data from patients with meningiomas, and the existence of specific estrogen receptors confirmed by immunochemical detection, may be important factors in a theory of oncogenesis.

Estrogen receptors in human prostate: evidence for multiple binding sites.

The existence of estrogen receptors in the human prostate has long been a controversial issue. This may be explained partly by the apparent heterogeneity of estrogen-binding sites in prostatic tissue. We herein report on multiple binding sites for estrogens in cytosol as well as nuclear preparations of human prostatic tissues. One class of binding sites corresponds to the classical, high affinity estrogen receptor; the Kd for [3H]estradiol binding to the receptor was approximately 0.10 nM and the binding was specific for estrogens. The second class of binding sites appeared to have a Kd for [3H]estradiol in the range of 5-10 nM. This second, lower affinity class of binding sites markedly influenced studies of the classical receptor even at low ligand concentrations. Saturation analysis should be performed over a wide range of ligand concentrations (0.05-10 nM) to allow separation of the two binding components. Quantitation of estrogen receptor by a single point assay cannot be carried out accurately unless the low affinity binding component can be blocked. Multiple binding sites for estradiol were observed in the cytosol as well as in the nuclear salt extractable and salt-resistant compartments of normal, benign hyperplastic, and cancerous human prostates. Normal peripheral and cancerous prostates contained significantly (P less than 0.01) higher amounts of cytosol estrogen receptor compared to benign hyperplastic tissue.

Steroid binding in the hypothalamus and pituitary.

Over the last few years, biochemical studies have established the existence of estrogen receptors in specific regions of the hypothalamus of adult male and female rats, presently indistinguishable from pituitary and uterine receptors, and of androgen receptors in the hypothalamus of the adult male. As yet, the existence of progesterone receptors is unproven (Kato, 1975).