RESUMO
Although hormones such as glucocorticoids have been broadly accepted in recent decades as general neuromodulators of memory processes, sex steroid hormones such as the potent oestrogen 17ß-oestradiol have been less well recognized by the scientific community in this capacity. The predominance of females in studies of oestradiol and memory and the general (but erroneous) perception that oestrogens are 'female' hormones have probably prevented oestradiol from being more widely considered as a key memory modulator in both sexes. Indeed, although considerable evidence supports a crucial role for oestradiol in regulating learning and memory in females, a growing body of literature indicates a similar role in males. This Review discusses the mechanisms of oestradiol signalling and provides an overview of the effects of oestradiol on spatial, object recognition, social and fear memories. Although the primary focus is on data collected in females, effects of oestradiol on memory in males will be discussed, as will sex differences in the molecular mechanisms that regulate oestrogenic modulation of memory, which may have important implications for the development of future cognitive therapeutics.
Assuntos
Encéfalo/fisiologia , Estradiol/fisiologia , Aprendizagem/fisiologia , Memória/fisiologia , Neurônios/fisiologia , Medo/fisiologia , Feminino , Humanos , Masculino , Caracteres Sexuais , Transdução de SinaisRESUMO
To date, studies of development have mainly focused on the embryonic stage and a short time thereafter. There has been little research on the whole life of an individual from childhood to aging and death. For the first time, we used noninvasive urinary proteome technology to track changes in several important developmental time points in a group of rats, covering 10 time points from childhood, adolescence, young adulthood, middle adulthood, and near-death in old age. Similar to previous studies on puberty, proteins were detected and they are involved in sexual or reproductive maturation, mature spermatozoa in seminiferous tubules (first seen), gonadal hormones, decline of estradiol, brain growth, and central nervous system myelination, and our differential protein enrichment pathways also included reproductive system development, tube development, response to hormone, response to estradiol, brain development, and neuron development. Similar to previous studies in young adults, proteins were detected and they are involved in musculoskeletal maturity, peak bone mass, development of the immune system, and growth and physical development, and our differential proteins enrichment pathways also included skeletal system development, bone regeneration, system development, immune system processes, myeloid leukocyte differentiation, and developmental growth. Studies on aging-related changes in neurons and neurogenesis have been reported, and we also found relevant pathways in aged rats, such as regulation of neuronal synaptic plasticity and positive regulation of long-term neuronal synaptic plasticity. However, at all time points throughout life, there were many biological pathways revealed by differential urinary protein enrichment involving multiple organs, tissues, systems, etc. that have not been mentioned in existing studies. This study shows comprehensive and detailed changes in rat lifetime development through the urinary proteome, helping to fill the gap in development research. Moreover, it provides a new approach to monitoring changes in human health and diseases of aging using the urinary proteome.
Assuntos
Estradiol , Proteoma , Criança , Masculino , Adolescente , Humanos , Ratos , Animais , Adulto Jovem , Adulto , Estradiol/fisiologia , EncéfaloRESUMO
By targeting the endocannabinoid system, delta-9-tetrahydrocannabinol (THC) modulates female motivated behaviours, influenced by sex hormones. Both medial preoptic nucleus (MPN) and ventromedial nucleus of the hypothalamus (VMN) are involved in the modulation of female sexual responses. The first triggers proceptivity, whereas the ventrolateral division of the latter (VMNvl) triggers receptivity. These nuclei are modulated by glutamate, which inhibits female receptivity, and GABA, which has a dichotomous action in female sexual motivation. Here, we evaluated the action of THC on the modulation of social and sexual behaviours, on signalling pathways of MPN and VMNvl and how sex hormones influence these parameters. Young ovariectomized female rats, given sex hormones (oestradiol benzoate, EB, and progesterone, P) and THC were used for behavioural testing and for immunofluorescence analyses of vesicular glutamate transporter 2 (VGlut2) and GAD (glutamic acid decarboxylase)67 expression. Results showed that females given EB + P exhibited a higher preference for male partner, as well as higher proceptivity and a higher receptivity than control or females given only EB. Females treated with THC presented similar responses in control or EB + P female rats and even more facilitated behavioural responses in EB females than the ones that did not receive THC. Immunofluorescence results in the MPN exhibited a decreased expression of GAD67 and VGlut2 in EB + THC-treated female rats. Within VMNvl of EB-primed rats no changes in the expression of both proteins were observed after THC exposure. This study demonstrates how the possible outcomes of endocannabinoid system instability within hypothalamic neuron connectivity can modify female rat sociosexual behaviour.
Assuntos
Dronabinol , Comportamento Sexual Animal , Ratos , Animais , Feminino , Masculino , Humanos , Dronabinol/farmacologia , Comportamento Sexual Animal/fisiologia , Endocanabinoides , Progesterona , Estradiol/farmacologia , Estradiol/fisiologia , Hipotálamo , OvariectomiaRESUMO
The sex steroid hormone 17ß-estradiol (estradiol) and its Estrogen Receptors (ERs) have been linked to modulation of anxiety-related and locomotor behaviors in female rodents. Research suggests that estradiol mitigates anxiety-related behaviors through activating Estrogen Receptor (ER)ß and increases locomotor behaviors through ERα. The influence of ERs on these behaviors cannot always be detected. Here we discuss two experiments in which we tested the hypothesis that anxiety-related behaviors would decrease after ERß activation and locomotor behaviors would increase after ERα activation, and also assessed the persistence of these behavioral effects by varying the timing of behavioral testing. Two cohorts of adult female ovariectomized rats were exposed to estradiol, the ERß agonist DPN, the ERα agonist PPT, or oil for four consecutive days. Body mass was assessed throughout as a positive control. In both cohorts, open field behaviors were assessed on the first day of exposure. In one cohort (Experiment 1), open field, light/dark box, and elevated plus maze behaviors were assessed on the final day of injections. In the second cohort (Experiment 2), these behaviors were assessed 24 h after the final exposure. As expected, significant differences in body mass were detected in response to estradiol and PPT exposure, validating the estradiol and ER manipulation. No significant differences were observed in anxiety-related or locomotor behaviors across treatment groups, indicating that the efficacy of these agonists as therapeutic agents may be limited. We review these results in the context of previous literature, emphasizing relevant variables that may obscure ER-related actions on behavior.
Assuntos
Estradiol , Receptores de Estrogênio , Ratos , Feminino , Animais , Humanos , Estradiol/farmacologia , Estradiol/fisiologia , Receptor beta de Estrogênio/agonistas , Receptor alfa de Estrogênio/agonistas , Ansiedade/tratamento farmacológico , Nitrilas , OvariectomiaRESUMO
INTRODUCTION: The nucleus accumbens core (NAcc) is a sexually differentiated brain region that is modulated by steroid hormones such as 17ß-estradiol (estradiol), with consequential impacts on relevant motivated behaviors and disorders such as addiction, anxiety, and depression. NAcc estradiol levels naturally fluctuate, including during the estrous cycle in adult female rats, which is analogous to the menstrual cycle in adult humans. Across the estrous cycle, excitatory synapse properties of medium spiny neurons rapidly change, as indicated by analysis of miniature excitatory postsynaptic currents (mEPSCs). mEPSC frequency decreases during estrous cycle phases associated with high estradiol levels. This decrease in mEPSC frequency is mimicked by acute topical exposure to estradiol. The identity of the estrogen receptor (ER) underlying this estradiol action is unknown. Adult rat NAcc expresses three ERs, all extranuclear: membrane ERα, membrane ERß, and GPER1. METHODS: In this brief report, we take a first step toward addressing this challenge by testing whether activation of ERs via acute topical agonist application is sufficient for inducing changes in mEPSC properties recorded via whole-cell patch clamp. RESULTS: An agonist of ERα induced large decreases in mEPSC frequency, while agonists of ERß and GPER1 did not robustly modulate mEPSC properties. CONCLUSIONS: These data provide evidence that activation of ERα is sufficient for inducing changes in mEPSC frequency and is a likely candidate underlying the estradiol-induced changes observed during the estrous cycle. Overall, these findings extend our understanding of the neuroendocrinology of the NAcc and implicate ERα as a primary target for future studies.
Assuntos
Núcleo Accumbens , Receptores de Estrogênio , Humanos , Ratos , Animais , Feminino , Núcleo Accumbens/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio , Estradiol/farmacologia , Estradiol/fisiologia , Sinapses/metabolismoRESUMO
INTRODUCTION: Although the fluid inhibitory effects of estradiol are well characterized, a dipsogenic role of the hormone was recently identified. In ovariectomized (OVX) rats, unstimulated water intake, in the absence of food, was increased after estradiol treatment. METHODS: The goals for these experiments were to further characterize the fluid enhancing effects of estradiol by determining the estrogen receptor subtype mediating the dipsogenic effect, examining saline intake, and testing for a dipsogenic effect of estradiol in male rats. RESULTS: Pharmacological activation of estrogen receptor beta (ERß) increased water intake, in the absence of food, and was associated with changes in postingestive feedback signals. Surprisingly, activation of ERα reduced water intake even in the absence of food. A follow-up study demonstrated that when food was available, co-activation of ERα and ERß reduced water intake, but when food was not available water intake was increased. In addition, in OVX rats, estradiol increased saline intake through changes in postingestive and orosensory feedback signals. Finally, although estradiol decreased water intake in male rats with access to food, estradiol had no effect on water intake in the absence of food. CONCLUSIONS: These results demonstrate that the dipsogenic effect is mediated by ERß, the fluid enhancing effects of estradiol generalize to saline, and is limited to females, which implies that a feminized brain is necessary for estradiol to increase water intake. These findings will aid in guiding future studies focused on elucidating the neuronal mechanisms that allow estradiol to both increase and decrease fluid intake.
Assuntos
Estradiol , Receptor beta de Estrogênio , Masculino , Ratos , Feminino , Animais , Humanos , Estradiol/farmacologia , Estradiol/fisiologia , Receptor alfa de Estrogênio , Seguimentos , Receptores de Estrogênio , OvariectomiaRESUMO
Corticotropin-releasing hormone (CRH) neurons are the primary neural population controlling the hypothalamic-pituitary-adrenal (HPA) axis and the secretion of adrenal stress hormones. Previous work has demonstrated that stress hormone secretion can be regulated by circulating levels of estradiol. However, the effect of estradiol on CRH neuron excitability is less clear. Here, we show that chronic estradiol replacement following ovariectomy increases two types of potassium channel currents in CRH neurons: fast inactivating voltage-gated A-type K+ channel currents (IA) and non-inactivating M-type K+ channel currents (IM). Despite the increase in K+ currents following estradiol replacement, there was no overall change in CRH neuron spiking excitability assessed with either frequency-current curves or current ramps. Together, these data reveal a complex picture whereby ovariectomy and estradiol replacement differentially modulate distinct aspects of CRH neuron and HPA axis function.
Assuntos
Hormônio Liberador da Corticotropina , Sistema Hipotálamo-Hipofisário , Feminino , Humanos , Hormônio Liberador da Corticotropina/farmacologia , Sistema Hipotálamo-Hipofisário/metabolismo , Estradiol/farmacologia , Estradiol/fisiologia , Sistema Hipófise-Suprarrenal/metabolismo , Neurônios/fisiologiaRESUMO
Estrogen hormones are implicated in a majority of breast cancers and estrogen receptor alpha (ER), the main nuclear factor mediating estrogen signaling, orchestrates a complex molecular circuitry that is not yet fully elucidated. Here, we investigated genome-wide DNA methylation, histone acetylation and transcription after estradiol (E2) deprivation and re-stimulation to better characterize the ability of ER to coordinate gene regulation. We found that E2 deprivation mostly resulted in DNA hypermethylation and histone deacetylation in enhancers. Transcriptome analysis revealed that E2 deprivation leads to a global down-regulation in gene expression, and more specifically of TET2 demethylase that may be involved in the DNA hypermethylation following short-term E2 deprivation. Further enrichment analysis of transcription factor (TF) binding and motif occurrence highlights the importance of ER connection mainly with two partner TF families, AP-1 and FOX. These interactions take place in the proximity of E2 deprivation-mediated differentially methylated and histone acetylated enhancers. Finally, while most deprivation-dependent epigenetic changes were reversed following E2 re-stimulation, DNA hypermethylation and H3K27 deacetylation at certain enhancers were partially retained. Overall, these results show that inactivation of ER mediates rapid and mostly reversible epigenetic changes at enhancers, and bring new insight into early events, which may ultimately lead to endocrine resistance.
Assuntos
Elementos Facilitadores Genéticos , Epigênese Genética , Estradiol/fisiologia , Ilhas de CpG , Metilação de DNA , Proteínas de Ligação a DNA/metabolismo , Dioxigenases/metabolismo , Código das Histonas , Humanos , Células MCF-7 , Receptores de Estrogênio/metabolismo , Transcrição GênicaRESUMO
Polycomb complexes have traditionally been prescribed roles as transcriptional repressors, though increasing evidence demonstrate they can also activate gene expression. However, the mechanisms underlying positive gene regulation mediated by Polycomb proteins are poorly understood. Here, we show that RING1B, a core component of Polycomb Repressive Complex 1, regulates enhancer-promoter interaction of the bona fide estrogen-activated GREB1 gene. Systematic characterization of RNA:DNA hybrid formation (R-loops), nascent transcription and RNA Pol II activity upon estrogen administration revealed a key role of RING1B in gene activation by regulating R-loop formation and RNA Pol II elongation. We also found that the estrogen receptor alpha (ERα) and RNA are both necessary for full RING1B recruitment to estrogen-activated genes. Notably, RING1B recruitment was mostly unaffected upon RNA Pol II depletion. Our findings delineate the functional interplay between RING1B, RNA and ERα to safeguard chromatin architecture perturbations required for estrogen-mediated gene regulation and highlight the crosstalk between steroid hormones and Polycomb proteins to regulate oncogenic programs.
Assuntos
Elementos Facilitadores Genéticos , Estradiol/fisiologia , Complexo Repressor Polycomb 1/metabolismo , Regiões Promotoras Genéticas , Estruturas R-Loop , Ativação Transcricional , Linhagem Celular , Cromatina/metabolismo , Receptor alfa de Estrogênio/metabolismo , Humanos , RNA/metabolismoRESUMO
Estradiol (E2) is a major hormone controlling women fertility, in particular folliculogenesis. This steroid, which is locally produced by granulosa cells (GC) within ovarian follicles, controls the development and selection of dominant preovulatory follicles. E2 effects rely on a complex set of nuclear and extra-nuclear signal transduction pathways principally triggered by its nuclear receptors, ERα and ERß. These transcription factors are differentially expressed within follicles, with ERß being the predominant ER in GC. Several ERß splice isoforms have been identified and display specific structural features, which greatly complicates the nature of ERß-mediated E2 signaling. This review aims at providing a concise overview of the main actions of E2 during follicular growth, maturation, and selection in human. It also describes the current understanding of the various roles of ERß splice isoforms, especially their influence on cell fate. We finally discuss how E2 signaling deregulation could participate in two ovarian pathogeneses characterized by either a follicular arrest, as in polycystic ovary syndrome, or an excess of GC survival and proliferation, leading to granulosa cell tumors. This review emphasizes the need for further research to better understand the molecular basis of E2 signaling throughout folliculogenesis and to improve the efficiency of ovarian-related disease therapies.
Assuntos
Estradiol/metabolismo , Ovário/metabolismo , Transdução de Sinais , Estradiol/fisiologia , Feminino , Humanos , Folículo Ovariano/metabolismo , Folículo Ovariano/fisiologia , Ovário/fisiologiaRESUMO
The steroid hormones are instrumental for the growth of mammary epithelial cells. Our previous study indicates that hormones regulate the expression of Rspondin-1 (Rspo1). Yet, the regulatory mechanism remains unknown. In the current study, we identify Amphiregulin (Areg) as a novel upstream regulator of Rspo1 expression mediating the hormonal influence. In response to hormonal signaling, Areg emanating from estrogen receptor (ER)-positive luminal cells, induce the expression of Rspo1 in ER-negative luminal cells. The paracrine action of Areg on Rspo1 expression is dependent on Egfr. Our data reveal a novel Estrogen-Areg-Rspo1 regulatory axis in the mammary gland, providing new evidence for the orchestrated action of systemic hormones and local growth factors.
Assuntos
Anfirregulina/fisiologia , Estradiol/fisiologia , Ciclo Estral/fisiologia , Regulação da Expressão Gênica/fisiologia , Glândulas Mamárias Animais/metabolismo , Progesterona/fisiologia , Trombospondinas/biossíntese , Anfirregulina/genética , Animais , Células Cultivadas , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/fisiologia , Cloridrato de Erlotinib/farmacologia , Estradiol/farmacologia , Ciclo Estral/genética , Feminino , Glândulas Mamárias Animais/citologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Cultura Primária de Células , Progesterona/farmacologia , RNA Interferente Pequeno/genética , Trombospondinas/genética , TranscriptomaRESUMO
While human vaginal pH in childbearing-age women is conclusively acidic, the mouse vaginal pH is reported as being near neutral. However, this information appears to be somewhat anecdotal with respect to vulvovaginal candidiasis, as such claims in the literature frequently lack citations of studies that specifically address this physiological factor. Given the disparate pH between mice and humans, the role of exogenous hormones and colonization by the fungal pathogen Candida albicans in shaping vaginal pH was assessed. Use of a convenient modified vaginal lavage technique with the pH indicator dye phenol red demonstrated that indeed vaginal pH was near neutral (7.2 ± 0.24) and was not altered by delivery of progesterone or estrogen in C57BL/6 mice. These trends were conserved in DBA/2 and CD-1 mouse backgrounds, commonly used in the mouse model of vaginitis. It was also determined that vaginal colonization with C. albicans did not alter the globally neutral vaginal pH over the course of one week. Construction and validation of a C. albicans reporter strain expressing GFPy, driven by the pH-responsive PHR1 promoter, confirmed the murine vaginal pH to be at least ≥6.0. Collectively, our data convincingly demonstrate a stable and conserved near neutrality of the mouse vaginal pH during vulvovaginal candidiasis and should serve as a definitive source for future reference. Implications and rationale for disparate pH in this model system are also discussed.
Assuntos
Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/fisiopatologia , Estradiol/fisiologia , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Vagina/fisiologia , Adulto , Animais , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBARESUMO
The roles of sex and sex-hormones on the metabolic consequences of intermittent hypoxia (IH, a reliable model of sleep apnea) are unknown. We used intact male or female mice and ovariectomized (OVX) females treated with vehicle (Veh) or estradiol (E2) and exposed to normoxia (Nx) or IH (6% O2, 10 cycles/h, 12 h/day, 2 wk). Mice were then fasted for 6 h, and we measured fasting glucose and insulin levels and performed insulin or glucose tolerance tests (ITT or GTT). We also assessed liver concentrations of glycogen, triglycerides (TGs), and expression levels of genes involved in aerobic or anaerobic metabolism. In males, IH lowered fasting levels of glucose and insulin, slightly improved glucose tolerance, but altered glucose tolerance in females. In OVX-Veh females, IH reduced fasting glucose and insulin levels and strongly impaired glucose tolerance. E2 supplementation reversed these effects and improved homeostasis model assessment of ß-cell function (HOMA-ß), a marker of pancreatic glucose-induced insulin released. IH decreased liver TG concentration in males and slightly increased glycogen in OVX-Veh females. Liver expression of glycolytic (Ldha) and mitochondrial (citrate synthase, Pdha1) genes was reduced by IH in males and in OVX-Veh females, but not in intact or OVX-E2 females. We conclude that 1) IH reduced fasting levels of glycemia in males and in ovariectomized females. 2) IH improves glucose tolerance only in males. 3) In females IH decreased glucose tolerance, this effect was amplified by ovariectomy, and reversed by E2 supplementation. 4) During IH exposures, E2 supplementation appears to improve pancreatic ß cells functions.NEW & NOTEWORTHY We assessed fasting glycemic control, and tolerance to insulin and glucose in male and female mice exposed to intermittent hypoxia. IH improves glucose tolerance in males but had opposite effects in females. This response was amplified following ovariectomy in females and prevented by estradiol supplementation. Metabolic consequences of IH differ between males and females and are regulated by estradiol in female mice.
Assuntos
Estradiol/fisiologia , Hipóxia/metabolismo , Animais , Glicemia/metabolismo , Metabolismo Energético/efeitos dos fármacos , Estradiol/farmacologia , Feminino , Teste de Tolerância a Glucose , Hipóxia/etiologia , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/fisiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia , Caracteres Sexuais , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/metabolismoRESUMO
Aromatase is the requisite and limiting enzyme in the production of estrogens from androgens. Estrogens synthesized centrally have more recently emerged as potent neuroprotectants in the vertebrate brain. Studies in rodents and songbirds have identified key mechanisms that underlie both; the injury-dependent induction of central aromatization, and the protective effects of centrally synthesized estrogens. Injury-induced aromatase expression in astrocytes occurs following a broad range of traumatic brain damage including excitotoxic, penetrating, and concussive injury. Responses to neural insult such as edema and inflammation involve signaling pathways the components of which are excellent candidates as inducers of this astrocytic response. Finally, estradiol from astrocytes exerts a paracrine neuroprotective influence via the potent inhibition of inflammatory pathways. Taken together, these data suggest a novel role for neural aromatization as a protective mechanism against the threat of inflammation and suggests that central estrogen provision is a wide-ranging neuroprotectant in the vertebrate brain.
Assuntos
Aromatase/metabolismo , Lesões Encefálicas/enzimologia , Encéfalo/enzimologia , Animais , Aromatase/genética , Astrócitos/enzimologia , Edema Encefálico/enzimologia , Estradiol/fisiologia , Feminino , Humanos , Inflamação/enzimologia , Masculino , Degeneração Neural/enzimologia , Neuroproteção/fisiologia , Aves Canoras/fisiologia , Regulação para CimaRESUMO
The gonadal steroids estradiol and progesterone exert critical suppressive and stimulatory actions upon the brain to control gonadotropin-releasing hormone (GnRH) release that drives the estrous/menstrual cycle. A simple model for understanding these interactions is proposed in which the activity of the "GnRH pulse generator" is restrained by post-ovulation progesterone secretion to bring about the estrus/luteal phase slowing of pulsatile gonadotropin release, while the activity of the "GnRH surge generator" is primed by the rising follicular phase levels of estradiol to generate the pre-ovulatory surge. The physiological fluctuations in estradiol levels across the cycle are considered to clamp the GnRH pulse generator output at a constant level. Independent pulse and surge generator circuitries regulate the excitability of different compartments of the GnRH neuron. As such, GnRH secretion through the cycle is determined simply by the summed influence of the estradiol-clamped, progesterone-regulated pulse and estradiol-regulated surge generators on the GnRH neuron.
Assuntos
Ciclo Estral/fisiologia , Retroalimentação Fisiológica/fisiologia , Hormônio Liberador de Gonadotropina/metabolismo , Ciclo Menstrual/fisiologia , Modelos Biológicos , Animais , Estradiol/farmacologia , Estradiol/fisiologia , Retroalimentação Fisiológica/efeitos dos fármacos , Feminino , Humanos , Periodicidade , Progesterona/farmacologia , Progesterona/fisiologiaRESUMO
The consolidation of long-term memory is influenced by various neuromodulators. One of these is estradiol, a steroid hormone that is synthesized both in peripheral endocrine tissue and in the brain, including the hippocampus. Here, we examine the evidence regarding the role of estradiol in the hippocampus, specifically, in memory formation and its effects on the molecular mechanisms underlying synaptic plasticity. We conclude that estradiol improves memory consolidation and, thereby, long-term memory. Previous studies have shown that it does this in three, interconnected ways: (1) via functional changes in excitatory activity, (2) signaling changes in calcium dynamics, protein phosphorylation and protein expression, and (3) structural changes to synaptic morphology. Through a functional network analysis of proteins affected by estradiol, we identify potential protein-protein interactions that further support a role for estradiol in modulating synaptic plasticity as well as highlight signaling pathways that may be involved in these changes within the hippocampus.
Assuntos
Estradiol/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Plasticidade Neuronal/fisiologia , Adulto , Animais , Estradiol/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Hipocampo/efeitos dos fármacos , Humanos , Masculino , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Fosforilação/fisiologia , Ratos , Receptores de Estrogênio/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Potenciais Sinápticos/efeitos dos fármacos , Potenciais Sinápticos/fisiologiaRESUMO
Women are vulnerable to developing mental disorders that are associated with circulating estrogens. Estrogens, especially 17ß-estradiol (E2), have a wide array of effects on the brain, affecting many behavioral endpoints associated with mental illness. By using a total estrogen receptor (ER) α knockout (KO), an ERα knock in/knock out (KIKO) that lacks a functional DNA-binding domain, and wild type (WT) controls treated with either oil or E2, we evaluated ERα signaling, dependent and independent of the estrogen response element (ERE), on avoidance behavior, social interactions and memory, and palatable ingestive behavior using the open field test, the elevated plus maze, the light dark box, the 3-chamber test, and palatable feeding. We found that ERα does not mediate control of anxiety-like behaviors but rather yielded differences in locomotor activity. In evaluating social preference and social recognition memory, we observed that E2 may modulate these measures in KIKO females but not KO females, suggesting that ERE-independent signaling is likely involved in sociability. Lastly, observations of palatable (high-fat) food intake suggested an increase in palatable eating behavior in oil-treated KIKO females. Oil-treated KO females had a longer latency to food intake, indicative of an anhedonic phenotype compared to oil-treated WT and KIKO females. We have observed that social-related behaviors are potentially influenced by ERE-independent ERα signaling and hedonic food intake requires signaling of ERα.
Assuntos
Aprendizagem da Esquiva , Receptor alfa de Estrogênio , Comportamento Alimentar , Interação Social , Animais , Comportamento Animal , Estradiol/farmacologia , Estradiol/fisiologia , Receptor alfa de Estrogênio/genética , Estrogênios/farmacologia , Feminino , Camundongos , Camundongos Knockout , Elementos de RespostaRESUMO
PURPOSE: Increasing age, male gender, and metabolic syndrome are associated with kidney stone formation. As sex hormones change with age, gender, and metabolic syndrome, we hypothesized that sex hormones may underlie the physiologic changes affecting stone formation. METHODS: We analyzed the relationships between testosterone, estradiol, and history of kidney stones using data from 10,193 participants in the Continuous National Health and Nutrition Examination Survey (NHANES) database from 2013-2016. We performed logistic regression analysis to analyze the predictive value of low testosterone and low estradiol on the history of kidney stones in both males and females. Self-reported history of kidney stone diagnosis was the outcome. RESULTS: After adjusting for risk factors known to be associated with nephrolithiasis such as age, race, BMI, and medical comorbidities including: gout, angina, coronary disease, stroke, asthma, hypertension, and diabetes, multiple regression analysis demonstrated that there is no independent association between sex hormones (testosterone and estradiol) and history of kidney stones in either males or females. CONCLUSIONS: There appears to be no association between sex hormones and history of kidney stones. Whether there is a more complex interaction of sex hormone levels and the shared association with factors such as metabolic syndrome requires additional investigation. Further studies matching menopausal status for women are necessary to further investigate the potential relationship between estrogen and kidney stones.
Assuntos
Estradiol/fisiologia , Cálculos Renais/etiologia , Testosterona/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Adulto JovemRESUMO
RNA polymerase II (Pol II) transcribes hundreds of kilobases of DNA, limiting the production of mRNAs and lncRNAs. We used global run-on sequencing (GRO-seq) to measure the rates of transcription by Pol II following gene activation. Elongation rates vary as much as 4-fold at different genomic loci and in response to two distinct cellular signaling pathways (i.e., 17ß-estradiol [E2] and TNF-α). The rates are slowest near the promoter and increase during the first ~15 kb transcribed. Gene body elongation rates correlate with Pol II density, resulting in systematically higher rates of transcript production at genes with higher Pol II density. Pol II dynamics following short inductions indicate that E2 stimulates gene expression by increasing Pol II initiation, whereas TNF-α reduces Pol II residence time at pause sites. Collectively, our results identify previously uncharacterized variation in the rate of transcription and highlight elongation as an important, variable, and regulated rate-limiting step during transcription.
Assuntos
RNA Polimerase II/metabolismo , RNA Mensageiro/biossíntese , Transdução de Sinais , Iniciação da Transcrição Genética , Estradiol/farmacologia , Estradiol/fisiologia , Humanos , Cinética , Células MCF-7 , Regiões Promotoras Genéticas , RNA Polimerase II/fisiologia , RNA Mensageiro/genética , Fatores de Transcrição/metabolismo , Sítio de Iniciação de Transcrição , Transcrição Gênica , Ativação Transcricional , Transcriptoma , Fator de Necrose Tumoral alfa/farmacologia , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
Most broadcast spawner corals have a vitellogenic phase that lasts at least 6 months. It is established that estrogen regulates vitellogenin synthesis in vertebrates. Although some research have been conducted on the physiological role of sex steroids in corals, little is known about their involvement in oocyte development. This study aimed to detect steroid hormones - progesterone, testosterone, and estradiol-17ß (E2) - in Acropora tenuis and study the relationships between vitellogenesis/vitellogenin synthesis and these steroids. This study also investigated the effect of E2 on vitellogenin synthesis in corals and identified steroidogenic enzymes in A. tenuis genome. Branches from tagged coral colonies were collected monthly from March to November. Histological observations showed that oocytes were vitellogenic from March to May (Stage IV and V), but not in June, and that gonads were occupied by immature oocytes in September (Stage I). Real-time qPCR revealed that vitellogenin (vg1 and vg2) transcript levels in coral branches were high in April and May, implying that corals actively underwent vitellogenesis during these months, and spawned before June. Liquid chromatography-mass spectrometry revealed that E2 could be detected in coral branches in March, April, and May, but not in June, whereas testosterone and progesterone did not fluctuate much in the same months. Immersing branches in E2-containing seawater failed to increase vitellogenin transcript levels. The results indicate that E2 is involved in oogenesis but does not positively regulate vitellogenin synthesis. Steroidogenic enzymes (except CYP19A) were identified in A. tenuis, suggesting that corals may endogenously synthesize progestogens and androgens from cholesterol.