Academic literature on the topic 'Estrogenic stress'

Estrogens are among important contributing factors to many sex differences in neuroendocrine regulation of energy homeostasis induced by stress. Research in this field is warranted since chronic stress-related psychiatric and metabolic disturbances continue to be top health concerns, and sex differences are witnessed in these aspects. For example, chronic stress disrupts energy homeostasis, leading to negative consequences in the regulation of emotion and metabolism. Females are known to be more vulnerable to the psychological consequences of stress, such as depression and anxiety, whereas males are more vulnerable to the metabolic consequences of stress. Sex differences that exist in the susceptibility to various stress-induced disorders have led researchers to hypothesize that gonadal hormones are regulatory factors that should be considered in stress studies. Further, estrogens are heavily recognized for their protective effects on metabolic dysregulation, such as anti-obesogenic and glucose-sensing effects. Perturbations to energy homeostasis using laboratory rodents, such as physiological stress or over-/under- feeding dietary regimen prevalent in today’s society, offer hints to the underlying mechanisms of estrogenic actions. Metabolic effects of estrogens primarily work through estrogen receptor α (ERα), which is differentially expressed between the sexes in hypothalamic nuclei regulating energy metabolism and in extrahypothalamic limbic regions that are not typically associated with energy homeostasis. In this review, we discuss estrogenic actions implicated in stress-induced sex-distinct metabolic disorders.

Phthalates are ubiquitous environmental pollutants associated with endocrine disruption and peroxisome proliferation in experimental animals. In yeasts exposed to environmental chemicals, including phthalates, alterations in cell growth, cellular morphology, and H2O2detoxification occur. Nutrient availability also influences diverse cellular processes. Differences in responses to environmental stress between Candida albicans and the model yeast, Saccharomyces cerevesiae , have been reported. In this study, we chose C. albicans as an alternate model for testing estrogen-like chemicals because of its high affinity estrogen-binding protein and, in contrast to S. cerevesiae, estrogens are not growth inhibitory for C. albicans. Cultures were grown in either yeast nitrogen dextrose (YND; phosphate limiting) or YNDP (YND plus 100 mmol/L inorganic phosphate). For chemical testing, 0.5% dibutylphthalate (DBP), 0.05% Tween 80, or a combination of the two (DBPT) were incorporated in growth media to investigate the effects of these estrogenic agents on cell proliferation, morphology, and catalase demonstration. We observed significant differences in cell growth related to DBP and changes in cell wall thickness related to both Tween 80 and phosphate. We describe ultrastructural changes including detachment of the outer yeast cell wall layer and presence of putative peroxisomes. Our findings support the proposal that C. albicans may be particularly suitable for use in studies involving cellular responses associated with exposure to estrogenic chemicals contained in complex mixtures.

Phytoestrogens are a large group of natural compounds found in more than 300 plants. They have a close structural similarity to estrogens, which allow them to bind to both estrogen receptors (ER), ERα and ERβ, presenting a weak estrogenic activity. Phytoestrogens have been described as antioxidant, anti-inflammatory, anti-thrombotic, anti-allergic, and anti-tumoral agents. Their role in cancer prevention has been well documented, although their impact on treatment efficiency is controversial. Several reports suggest that phytoestrogens may interfere with the effect of anti-cancer drugs through the regulation of oxidative stress and other mechanisms. Furthermore, some phytoestrogens could exert a protective effect on healthy cells, thus reducing the secondary effects of cancer treatment. In this review, we have studied the recent research in this area to find evidence for the role of phytoestrogens in cancer prevention and therapy efficacy.

Obesity has become a major health problem in many parts of the world. Estrogens are known to reduce adipose tissue mass in both humans and animals but the molecular mechanisms are not well characterized. We used gene expression profiling to study long-term effects of estrogen on gene expression in mouse white adipose tissue and hypothalamus. Overall, the effects of estrogen on hypothalamic gene expression were much smaller than the corresponding effects on white adipose tissue gene expression. We characterize in detail estrogenic regulation of glutathione peroxidase 3 (GPX3). Our studies suggest that GPX3 is a direct estrogen receptor α target gene in white adipose tissue. Since obesity is correlated with oxidative stress, and GPX3 has been demonstrated to be lower in obesity and higher after weight loss, we hypothesize that GPX3 is one important mediator of effects of estrogen in relation to fat mass. Additional genes that were affected by estrogen in adipose tissue include cell death-inducing DNA fragmentation factor, α-subunit-like effector A (CIDEA), a gene shown to be related to body fat in mice. We conclude that estrogen has large effects on gene expression in white adipose tissue and hypothesize that GPX3 and CIDEA could be important mediators of the effects of estrogen on fat mass.

Glucocorticoids (GCs) and estrogen can modulate neuron death and dysfunction during neurological insults. Glucocorticoids are adrenal steroids secreted during stress, and hypersecretion of GCs during cerebral ischemia compromises the ability of hippocampal and cortical neurons to survive. In contrast, estrogen can be neuroprotective after cerebral ischemia. Here we evaluate the protective potential of a herpes viral vector expressing a chimeric receptor (ER/GR), which is composed of the ligand-binding domain of the GC receptor (GR) and the DNA-binding domain of the estrogen receptor-α (ER). This novel receptor can transduce an endangering GC signal into a protective estrogenic one. Using an in vitro oxygen glucose deprivation model (OGD), GCs exacerbated neuron death in primary cortical cultures, and this worsening effect was completely blocked by ER/GR expression. Moreover, blocking GC actions with a vector expressing a dominant negative GC receptor promoted neuron survival during postischemia, but not preischemia. Thus, gene therapeutic strategies to modulate GC and estrogen signaling can be beneficial during an ischemic insult.

There is growing concern regarding the health and safety issues of endocrine-disrupting chemicals (EDCs). Long-term exposure to EDCs has serious adverse health effects through both hormone-direct and hormone-indirect ways. Accordingly, some EDCs can be a pathogen and an inducer to the susceptibility of disease, even if they have a very low affinity on the estrogen receptor, or no estrogenic effect. Endoplasmic reticulum (ER) stress recently attracted attention in this research area. Because ER and ER stress could be key regulators of the EDC’s adverse effects, such as the malfunction of the organ, as well as the death, apoptosis, and proliferation of a cell. In this review, we focused on finding evidence which shows that EDCs could be a trigger for ER stress and provide specific examples of EDCs, which are known to cause ER stress currently.

Abstract Hydrogen sulfide, generated in the myocardium predominantly via cystathionine-γ-lyase (CSE), is cardioprotective. Our previous study has shown that estrogens enhance CSE expression in myocardium of female rats. The present study aims to explore the mechanisms by which estrogens regulate CSE expression, in particular to clarify the role of estrogen receptor subtypes and the transcriptional factor responsible for the estrogenic effects. We found that either the CSE inhibitor or the CSE small interfering RNA attenuated the protective effect of 17β-estradiol (E2) against H2O2- and hypoxia/reoxygenation-induced injury in primary cultured neonatal cardiomyocytes. E2 stimulates CSE expression via estrogen receptor (ER)-α both in cultured cardiomyocytes in vitro and in the myocardium of female mice in vivo. A specificity protein-1 (Sp-1) consensus site was identified in the rat CSE promoter and was found to mediate the E2-induced CSE expression. E2 increases ERα and Sp-1 and inhibits microRNA (miR)-22 expression in myocardium of ovariectomized rats. In primary cardiomyocytes, E2 stimulates Sp-1 expression through the ERα-mediated down-regulation of miR-22. It was confirmed that both ERα and Sp-1 were targeted by miR-22. In the myocardium of ovariectomized rats, the level of miR-22 inversely correlated to CSE, ERα, Sp-1, and antioxidant biomarkers and positively correlated to oxidative biomarkers. In summary, this study demonstrates that estrogens stimulate Sp-1 through the ERα-mediated down-regulation of miR-22 in cardiomyocytes, leading to the up-regulation of CSE, which in turn results in an increase of antioxidative defense. Interaction of ERα, miR-22, and Sp-1 may play a critical role in the control of oxidative stress status in the myocardium of female rats.

Background/Aims: estrogens and phytoestrogens exert hepatoprotection through mechanisms not clearly examined yet. Here, we investigated the protective effects exerted by 17β-estradiol and genistein against oxidative stress in hepatocytes and hepatic stellate cells (HSCs) and the involvement of specific receptors and the intracellular signalling. Methods: Huh7.5 and LX-2, alone or in co-culture with Huh7.5, were treated with 17β-estradiol and genistein alone or in the presence of menadione and of estrogen receptors (ERs) and G protein-coupled-estrogenic-receptors (GPER) blockers. Cell viability, mitochondrial membrane potential and oxidant/antioxidant system were measured by specific kits. Western Blot was used for the analysis of Akt and p38-mitogen-activated-protein kinases (MAPK) activation and α-smooth-muscle actin expression. Results: In Huh7.5, 17β-estradiol and genistein prevented the effects of peroxidation by modulating Akt and p38MAPK activation. Similar antioxidant and protective findings were obtained in LX-2 of co-culture experiments, only. ERs and GPER blockers were able to prevent the effects of 17β-estradiol and genistein. Conclusion: In Huh7.5 and LX-2, 17β-estradiol and genistein counteract the effects of peroxidation through the involvement of ERs and GPER and by an intracellular signalling related to Akt and p38MAPK. As concerning LX-2, paracrine factors released by Huh7.5 play a key role in protection against oxidative stress.

The prevalence of diabetes is lower in premenopausal women, especially diabetic syndromes with insulin deficiency, suggesting that the female hormone 17β-estradiol protects pancreatic β-cell function. In classical rodent models of β-cell failure, 17β-estradiol at physiological concentrations protects pancreatic β-cells against lipotoxicity, oxidative stress, and apoptosis. In this review, we integrate evidence showing that estrogens and their receptors have direct effects on islet biology. The estrogen receptor (ER)-α, ERβ, and the G-protein coupled ER are present in β-cells and enhance islet survival. They also improve islet lipid homeostasis and insulin biosynthesis. We also discuss evidence that ERs modulate insulin sensitivity and energy homeostasis, which indirectly alter β-cell biology in diabetic and obese conditions.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
A diminuição das concentrações plasmáticas de estrógeno está intimamente relacionada com o aumento do estresse oxidativo e a diminuição da massa muscular em idosos. A terapêutica hormonal estrogênica (THE) e o treinamento de força (TF) apresentam resultados efetivos sobre a manutenção do tecido muscular em idosos. No entanto, os mecanismos responsáveis pelas melhorias induzias por ambas as intervenções são pouco elucidados. Nesse sentido, avaliamos os efeitos da THE, do TF e a associação sobre a manutenção do tecido muscular esquelético de ratas periestropausadas. Ratas Wistar (18 meses) foram distribuídas em: Grupo não treinado (NT-Veh), Grupo NT tratado com a THE (NT-E2), Grupo TF (TF-Veh) e Grupo TF-E2. Os animais receberam a THE (17β estradiol; 2 x semana; 25 µg/kg/administração) e/ou praticaram TF (3 x semana; 80% sobrecarga) durante 16 semanas. A THE e o TF induzem benefícios ao tecido muscular esquelético de ratas periestropausadas, no entanto, por diferentes maneiras. Enquanto a THE induziu diminuição do estresse oxidativo muscular (Dihidroetidina), o TF resultou em melhoras significativas na função muscular, no sistema antioxidante muscular (Catalase) e na expressão de miRNAs (206, 146b e 133a). Já a interação das intervenções resultou em melhora no estado redox (Sirt1, Sirt3, PGC-1α, COXIV), na responsividade dos receptores estrogênicos (ERα, ERβ e GPR30), e atividade de vias de sinalização do tecido muscular (IGF-1/Akt-1/mTOR). Além disso, as intervenções de maneira isolada ou em associação, levaram ao aumento no percentual de fibras glicolíticas e redução das oxidativas. Sugerimos que a aderências das intervenções (associadas ou não) possam minimizar/atenuar a perda da massa muscular observada em fases tardias durante o processo de envelhecimento.
The decrease of estrogen (E2) circulating levels is strongly related to increased oxidative stress and the loss of muscle mass in elderly. The hormone replacement therapy (HRT) and strength training (ST) are the main effective interventions to prevent the loss of muscle mass, however, the mechanisms involved in interventions-induced benefits are not well elucidated. In this sense we evaluate the effect of HRT, ST and association on skeletal muscle maintenance of periestropaused rats. Female Wistar rats (18 months old) were randomly assigned into: non-exercised and non-treated group (NE-Veh), NE treated group (NE-E2), exercised and non-treated group (ST-Veh) and ST-E2 group. The animals received the HRT (17β estradiol; 2 x week; 50 µg/kg/week) and/or performed ST (3 x week, 80% overload) for 16 weeks. The HRT and ST promoted beneficial effects on skeletal muscle of periestropaused rats, however, by different manners. While HRT treatment leaves the reduction of oxidative stress (Dihidroetidine), the ST resulted in significate improvement on skeletal muscle function, in skeletal muscle antioxidant system (Catalase) and in miRNAs expression (2016, 146b and 133a). Already, the association of interventions resulted in improvement of redox state (Sirt1, Sirt3, PGC-1α, COXIV), in estrogen receptor responsiveness (ERα, ERβ and GPR30) and the activity of skeletal muscle signaling pathways (IGF-1/Akt-1/mTOR). In addition, the interventions, isolated or combinated, leaves an increase of the percentage of glycolytic fibers and reduced percentage of oxidative fibers. We suggest that the adherence to interventions (combinated or not) could minimize/attenuate the loss of skeletal muscle mass observed in later phases of aging process.
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Les travaux présentés dans cette thèse proposent d’évaluer l'impact d’un stress oestrogénique, durant des phases clés du cycle de vie des poissons (développement précoce et gamétogénèse), dans un contexte de changement global, tel que simulé par le scénario RCP8.5 du GIEC à l'horizon 2100 (+3 °C et -0.4 unité pH). Elle s’appuie sur une expérimentation en milieu contrôlé menée sur l’épinoche à trois épines (Gasterosteus aculeatus), permettant d’une part, l'exposition à des scénarios climatiques différents (actuel et RCP8.5) sur tout le cycle de vie de cette espèce et d’autre part, de combiner ce stress climatique à un stress oestrogénique (17α-ethynylestradiol = EE2 ; 15 ng.l-1) pendant les stades embryo-larvaires et en fin de gamétogénèse. L’impact du stress climatique, ou du multi-stress, a été abordé par une approche intégrative, s'appuyant sur des analyses physiologiques, biochimiques et moléculaires, permettant d’observer les effets sur la croissance, la reproduction et la survie à différents niveaux biologiques. En résumé, cette étude montre que des conditions de températures plus élevées et de pH plus bas augmentent les coûts métaboliques, affectant la croissance des juvéniles. Cet effet sur la croissance est accentué lors d’une contamination précoce à l’EE2. Au stade adulte, les coûts métaboliques générés par le stress climatique, impactent la maturité sexuelle et le succès reproducteur (diminution du nombre de femelles capables de se reproduire, retard et réduction de la période de ponte, maturation ovocytaire et qualité des oeufs amoindries). Ces effets ne sont pas modulés par le stress oestrogénique supplémentaire, appliqué en fin de gamétogénèse. Toutefois, la contamination pendant les stades précoces a entraîné des effets durables, comme une féminisation des mâles et une perturbation de l'axe de la reproduction, sans modulation par la condition climatique. Enfin, les deux principaux résultats sur la survie concernent, deux périodes : 1- En condition de stress climatique, un pic de mortalité a été observé après la reproduction, associé à la prolifération de Vibrio rotiferianus et à un état physiologique plus vulnérable des épinoches en période de post-reproduction et de températures plus élevées. 2- En condition de multistress où une mortalité totale des larves issues de parents contaminés à l’EE2 a été constatée suggérant un rôle crucial de l’exposition des géniteurs sur les réponses de la descendance. Ces travaux soulignent l’intérêt de considérer le multi-stress sur l’entièreté du cycle de vie pour estimer la vulnérabilité des espèces aquatiques dans un environnement futur
The work presented in this thesis aims to evaluate the effects of estrogenic stress during key phases of the fish life cycle (early development and gametogenesis) in the context of global change as simulated by the IPCC RCP8.5 scenario for the year 2100 (+3 °C and -0.4 pH units). It is based on a controlled environment experiment carried out on the three-spined stickleback (Gasterosteus aculeatus), which allows exposure to different climate scenarios (current and RCP8.5) throughout the life cycle of this species and, in addition, to combine this climatic stress with estrogenic stress (17α-ethynylestradiol = EE2 ; 15 ng.l-1) during the embryonic-larval stages and at the end of gametogenesis. The effects of climatic stress, or multistress, were addressed by an integrative approach based on physiological, biochemical and molecular analyses, allowing the observation of effects on growth, reproduction and survival at different biological levels. In conclusion, this study shows that higher temperature and lower pH conditions increase metabolic costs and thus affect juvenile growth. This effect on growth is exacerbated by early contamination with EE2. At the adult stage, the metabolic costs generated by climatic stress affect sexual maturity and reproductive success (reduction in the number of reproductive females, delay and reduction in the spawning period, impaired oocyte maturation and egg quality). These effects are not modulated by additional estrogenic stress applied at the end of gametogenesis. On the other hand, contamination during early stages resulted in permanent effects such as feminisation of males and disruption of the reproductive axis, without modulation by climatic conditions. Finally, the two main results on survival concern two periods: 1- Under climatic stress conditions, a post-reproductive mortality peak wasobserved, associated with the proliferation of Vibrio rotiferianus and a more vulnerable physiological state of the sticklebacks during the post-reproductive period and at higher temperatures. 2- Under multistress conditions, a total mortality of larvae from EE2-contaminated parents was observed, suggesting a critical role of parental exposure on offspring responses. This work highlights the importance of considering multi-stress throughout the life cycle to assess the vulnerability of aquatic species in a future environment

The present study was conducted to determine the effect of differential endogenous estrogen exposure in rats on stress-induced changes in spatial working memory. Subjects comprised male (n=8) and female (n=10) Sprague-Dawley rats, which were trained to complete a T maze, delayed alternation task. Performance was scored as a percentage of trials during which the correct maze arm was selected. Subjects scores were recorded after 1 and 2 hours of restraint stress, as well as after 1 hour of unimpeded movement in a cage placed in the testing room. Restraint stress was effected through physical confinement within plastic, cylindrical tubing. Female subjects underwent each of the testing conditions twice, during periods of high and low endogenous estrogen exposure, as ascertained by microscopic examination of vaginal epithelial cells for estrous cycle stage determination. Females in proestrus (elevated endogenous estrogen exposure) subjected to 1 hour of restraint performed significantly worse than their baseline scores (p=0.0017) or females in estrus (low endogenous estrogen exposure) after 1 hour of restraint (p=0.00014). After 1 hour of restraint, females in proestrus also committed an increased rate of perseverative errors compared to females in estrus, although this increase did not achieve statistical significance (p=0.06). No appreciable differences existed among subject groups in baseline performance or subsequent to 2 hours of restraint stress. Resultant data indicate impaired working memory among female rats under conditions of stress in the context of elevated endogenous estrogen exposure. This study, then, suggests a potential synergistic effect of stress and estrogen in compromising prefrontal cortex function and, therefore, may lend insight into the observed sex-related disparity in the incidence of major depressive disorder and other anxiety-related mood disorders.

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior
O desempenho fisiolÃgico da atividade celular requer um equilÃbrio entre a produÃÃo de espÃcies de radicais livres e a sua desativaÃÃo por agentes reguladores e protetores. Quando esse equilÃbrio à quebrado, surge o estresse oxidativo. Diversos estudos experimentais utilizando estrÃgenos para a induÃÃo de distÃrbios ovarianos e metabÃlicos, com destaque para a SÃndrome dos OvÃrios PolicÃsticos (SOP), estÃo disponÃveis na literatura cientÃfica. A Metformina (MTF) à um anti-hiperglicemiante, frequentemente utilizado para tratamento da SOP, permitindo a restauraÃÃo da ciclicidade menstrual, induÃÃo da ovulaÃÃo e o aumento da ocorrÃncia de gestaÃÃo. Na Medicina Tradicional Chinesa, a Acupuntura (Ac) e a Eletroacupuntura (EAc) sÃo utilizadas na promoÃÃo do equilÃbrio orgÃnico, mediante estÃmulo de vias nervosas produtoras de neurotransmissores especÃficos, resultando em uma resposta anti-inflamatÃria, analgÃsica e reguladora autonÃmica. Neste estudo, objetivou-se avaliar os efeitos da MTF, da Ac e da EAc aplicadas nos acupontos Zusanli (E36) e Sanyjiao (BP6), sobre o estresse oxidativo sistÃmico e local, inflamaÃÃo e glicemia em ratas sadias submetidas a estÃmulo estrogÃnico. No experimento, 42 ratas foram distribuÃdas aleatoriamente em sete grupos. Em 30 ratas (grupos G1C+, G2M, G3Ac, G4EAc2, G5EAc100) administrou-se estrogÃnio (valerato de estradiol, 4mg, dose Ãnica). Os dois grupos restantes serviram como controles negativos (G6M, G7) e nÃo receberam estÃmulo estrogÃnico. ApÃs 60 dias, iniciou-se a segunda fase do estudo, compreendendo um perÃodo de dez dias. A Ac e EAc (2/100Hz), foram aplicadas, sob anestesia, em dias alternados, por 20 minutos, durante nove dias nos grupos G3Ac, G4EAc2, G5EAc100; MTF foi administrada diariamente, por gavagem, durante nove dias aos grupos G2M e G6M. No 10 dia desta fase, todas as ratas foram submetidas ao teste de tolerÃncia oral a glicose,e avaliadas em trÃs ocasiÃes: antes do inicio do teste e apÃs 60/120 minutos; seguiu-se a laparotomia, sob anestesia, para coleta de sangue na artÃria aorta abdominal e exÃrese do Ãtero e ovÃrios para exames a seguir: dosagem de SubstÃncias Reativas ao Ãcido TiobarbitÃrico (TBARs), da Glutationa (GSH) reduzida, da Mieloperoxidase (MPO) e da histopatologia ovariana. Os resultados mostraram um aumento significativo das concentraÃÃes plasmÃticas de GSH nos grupos G3Ac, G4EAc2 e G5EAc100 comparados ao G1 (24,50Â1,59 vs 20,30Â0,43, p<0,05; 30,80Â3,22 e 40,30Â3,48 vs 20,30Â0,43, p<0,0001), respectivamente. Houve aumento significante das concentraÃÃes de GSH no tecido ovariano das ratas tratadas com EAc2/100 (47,00Â17,60 vs 25,70Â2,33, p<0,05 e 63,00Â12,40 vs 25,70Â2,33, p<0,0001). A EAc2/100 promoveu aumento significante nas concentraÃÃes plasmÃticas de TBARS (0,231 0,09 vs 0,054Â0,07, p<0,05 e 0,296Â0,09 vs 0,054Â0,07, p<0,001). Houve reduÃÃo significante na atividade da MPO ovariana nos grupos G4EAc2 e G5EAc100 (0,59Â0,21 vs 1,76Â0,31, p<0,05 e 0,65Â0,05 vs 1,76Â0,31, p<0,0001). A administraÃÃo de MTF nÃo promoveu alteraÃÃes nos marcadores oxidativos ou inflamatÃrios. NÃo mostrou alteraÃÃo da glicemia em nenhum dos grupos estudados. No estudo do nÃmero de folÃculos, corpos lÃteos e cistos foliculares nÃo houve diferenÃa significativa entre todos os grupos estudados, ao exame histopatolÃgico. Conclui-se que a aplicaÃÃo de EAc2/100Hz promove proteÃÃo local e sistÃmica sobre o estresse oxidativo por aumento das concentraÃÃes de GSH, alÃm de reduzir o estado inflamatÃrio no ovÃrio de ratas sadias submetidas a estimulo estrogÃnico.
O desempenho fisiolÃgico da atividade celular requer um equilÃbrio entre a produÃÃo de espÃcies de radicais livres e a sua desativaÃÃo por agentes reguladores e protetores. Quando esse equilÃbrio à quebrado, surge o estresse oxidativo. Diversos estudos experimentais utilizando estrÃgenos para a induÃÃo de distÃrbios ovarianos e metabÃlicos, com destaque para a SÃndrome dos OvÃrios PolicÃsticos (SOP), estÃo disponÃveis na literatura cientÃfica. A Metformina (MTF) à um anti-hiperglicemiante, frequentemente utilizado para tratamento da SOP, permitindo a restauraÃÃo da ciclicidade menstrual, induÃÃo da ovulaÃÃo e o aumento da ocorrÃncia de gestaÃÃo. Na Medicina Tradicional Chinesa, a Acupuntura (Ac) e a Eletroacupuntura (EAc) sÃo utilizadas na promoÃÃo do equilÃbrio orgÃnico, mediante estÃmulo de vias nervosas produtoras de neurotransmissores especÃficos, resultando em uma resposta anti-inflamatÃria, analgÃsica e reguladora autonÃmica. Neste estudo, objetivou-se avaliar os efeitos da MTF, da Ac e da EAc aplicadas nos acupontos Zusanli (E36) e Sanyjiao (BP6), sobre o estresse oxidativo sistÃmico e local, inflamaÃÃo e glicemia em ratas sadias submetidas a estÃmulo estrogÃnico. No experimento, 42 ratas foram distribuÃdas aleatoriamente em sete grupos. Em 30 ratas (grupos G1C+, G2M, G3Ac, G4EAc2, G5EAc100) administrou-se estrogÃnio (valerato de estradiol, 4mg, dose Ãnica). Os dois grupos restantes serviram como controles negativos (G6M, G7) e nÃo receberam estÃmulo estrogÃnico. ApÃs 60 dias, iniciou-se a segunda fase do estudo, compreendendo um perÃodo de dez dias. A Ac e EAc (2/100Hz), foram aplicadas, sob anestesia, em dias alternados, por 20 minutos, durante nove dias nos grupos G3Ac, G4EAc2, G5EAc100; MTF foi administrada diariamente, por gavagem, durante nove dias aos grupos G2M e G6M. No 10 dia desta fase, todas as ratas foram submetidas ao teste de tolerÃncia oral a glicose,e avaliadas em trÃs ocasiÃes: antes do inicio do teste e apÃs 60/120 minutos; seguiu-se a laparotomia, sob anestesia, para coleta de sangue na artÃria aorta abdominal e exÃrese do Ãtero e ovÃrios para exames a seguir: dosagem de SubstÃncias Reativas ao Ãcido TiobarbitÃrico (TBARs), da Glutationa (GSH) reduzida, da Mieloperoxidase (MPO) e da histopatologia ovariana. Os resultados mostraram um aumento significativo das concentraÃÃes plasmÃticas de GSH nos grupos G3Ac, G4EAc2 e G5EAc100 comparados ao G1 (24,50Â1,59 vs 20,30Â0,43, p<0,05; 30,80Â3,22 e 40,30Â3,48 vs 20,30Â0,43, p<0,0001), respectivamente. Houve aumento significante das concentraÃÃes de GSH no tecido ovariano das ratas tratadas com EAc2/100 (47,00Â17,60 vs 25,70Â2,33, p<0,05 e 63,00Â12,40 vs 25,70Â2,33, p<0,0001). A EAc2/100 promoveu aumento significante nas concentraÃÃes plasmÃticas de TBARS (0,231 0,09 vs 0,054Â0,07, p<0,05 e 0,296Â0,09 vs 0,054Â0,07, p<0,001). Houve reduÃÃo significante na atividade da MPO ovariana nos grupos G4EAc2 e G5EAc100 (0,59Â0,21 vs 1,76Â0,31, p<0,05 e 0,65Â0,05 vs 1,76Â0,31, p<0,0001). A administraÃÃo de MTF nÃo promoveu alteraÃÃes nos marcadores oxidativos ou inflamatÃrios. NÃo mostrou alteraÃÃo da glicemia em nenhum dos grupos estudados. No estudo do nÃmero de folÃculos, corpos lÃteos e cistos foliculares nÃo houve diferenÃa significativa entre todos os grupos estudados, ao exame histopatolÃgico. Conclui-se que a aplicaÃÃo de EAc2/100Hz promove proteÃÃo local e sistÃmica sobre o estresse oxidativo por aumento das concentraÃÃes de GSH, alÃm de reduzir o estado inflamatÃrio no ovÃrio de ratas sadias submetidas a estimulo estrogÃnico.
The physiological performance of cellular activity requires a balance between the production of free radicals and their deactivation by regulators and surge protectors. When this balance is broken, the oxidative stress takes place. Several experimental studies using estrogens to induction of ovarian and metabolic disorders, with emphasis on the polycystic ovary syndrome (PCOS), are available in the scientific literature.The Metformin (MTF) is a medication used for diabetic patients, and is often used for treatment of Polycystic Ovary Syndrome (PCOS), allowing restoration of cyclicality, induction of ovulation and menstruation. Acupuncture (Ac) and Electroacupuncture (EAc) are used in Traditional Chinese Medicine for the promotion of organic equilibrium, through stimulation of nerve pathways producing specific neurotransmitters, resulting in an antinflammatory, analgesic and autonomic regulatory response.This study aimed at evaluating the effects of MTF and Ac and EAc, applied on Zusanli (E36) and Sanyjiao (BP6) acupoints on the local and systemic oxidative stress, inflammation and blood glucose levels in healthy rats submitted to estrogenic stimulation. In the experiment, 42 rats were distributed randomly assigned into seven groups. In the experiment, 42 rats were randomly assigned into seven groups. Thirty rats (groups G1C , G2M, G3Ac, G4EAc2, G5EAc100) were administered estrogen (estradiol valerate, 4mg, single dose). The two remaining groups served as negative controls (G6M, G7) and received no estrogenic stimulation. After 60 days, began the second phase of the study, comprising a ten-day period. Ac and EAc (2/100Hz), were applied for 20 minutes, under anesthesia, in alternated days during nine days, to groups G3Ac, G4EAc2, and G5EAc100. MTF was given daily during nine days by gavage to G2M and G6M groups. On the 10th day, all rats were subjected to the oral glucose tolerance test, and evaluated on three occasions: before the beginning of the test and after 60/120 minutes. Next, followed laparotomy, under anesthesia, for collection of blood from the abdominal aorta artery and harvesting of uterus and ovary for examination. Parameters analysed included the Thiobarbituric Acid Reactive Substances (TBARS), reduced Glutathione (GSH), Myeloperoxidase (MPO), and ovarian histopathology. At the end of the experiment plasma concentrations of GSH increased significantly in G3Ac, G4EAc2 and G5EAc100 groups compared to G1 (24.50Â1.59 vs 20.30Â0.43, p<0.05; 30.80Â3.22 and 40.30Â3.48 vs 20.30Â0.43, p<0.0001) respectively. There has been a significant increase in concentrations of GSH in ovarian tissue of rats treated with EAc2/100 (47.00Â17.60 vs 25.70Â2.33, p<.005 and 63.00Â12,40 vs 25,70Â2.33, p<0.0001). There was a significant reduction in ovarian MPO activity in groups G4EAc2 and G5EAc100 (0.59Â0.21 vs 1.76Â0.31, p<0.05 and 0.65Â0.05 vs 1.76Â0.31p<0.001). MTF did not promote changes in oxidative or inflammatory markers. There was no change in blood glucose levels in any of the groups studied. Corpus luteum and follicular cysts number were not different in all groups. It is concluded that EAc2/100Hz treatments promote systemic and local protection on oxidative stress by increasing GSH concentrations and by reducing the inflammatory status in the ovary of healthy rats submitted to estrogenic stimulation.
The physiological performance of cellular activity requires a balance between the production of free radicals and their deactivation by regulators and surge protectors. When this balance is broken, the oxidative stress takes place. Several experimental studies using estrogens to induction of ovarian and metabolic disorders, with emphasis on the polycystic ovary syndrome (PCOS), are available in the scientific literature.The Metformin (MTF) is a medication used for diabetic patients, and is often used for treatment of Polycystic Ovary Syndrome (PCOS), allowing restoration of cyclicality, induction of ovulation and menstruation. Acupuncture (Ac) and Electroacupuncture (EAc) are used in Traditional Chinese Medicine for the promotion of organic equilibrium, through stimulation of nerve pathways producing specific neurotransmitters, resulting in an antinflammatory, analgesic and autonomic regulatory response.This study aimed at evaluating the effects of MTF and Ac and EAc, applied on Zusanli (E36) and Sanyjiao (BP6) acupoints on the local and systemic oxidative stress, inflammation and blood glucose levels in healthy rats submitted to estrogenic stimulation. In the experiment, 42 rats were distributed randomly assigned into seven groups. In the experiment, 42 rats were randomly assigned into seven groups. Thirty rats (groups G1C , G2M, G3Ac, G4EAc2, G5EAc100) were administered estrogen (estradiol valerate, 4mg, single dose). The two remaining groups served as negative controls (G6M, G7) and received no estrogenic stimulation. After 60 days, began the second phase of the study, comprising a ten-day period. Ac and EAc (2/100Hz), were applied for 20 minutes, under anesthesia, in alternated days during nine days, to groups G3Ac, G4EAc2, and G5EAc100. MTF was given daily during nine days by gavage to G2M and G6M groups. On the 10th day, all rats were subjected to the oral glucose tolerance test, and evaluated on three occasions: before the beginning of the test and after 60/120 minutes. Next, followed laparotomy, under anesthesia, for collection of blood from the abdominal aorta artery and harvesting of uterus and ovary for examination. Parameters analysed included the Thiobarbituric Acid Reactive Substances (TBARS), reduced Glutathione (GSH), Myeloperoxidase (MPO), and ovarian histopathology. At the end of the experiment plasma concentrations of GSH increased significantly in G3Ac, G4EAc2 and G5EAc100 groups compared to G1 (24.50Â1.59 vs 20.30Â0.43, p<0.05; 30.80Â3.22 and 40.30Â3.48 vs 20.30Â0.43, p<0.0001) respectively. There has been a significant increase in concentrations of GSH in ovarian tissue of rats treated with EAc2/100 (47.00Â17.60 vs 25.70Â2.33, p<.005 and 63.00Â12,40 vs 25,70Â2.33, p<0.0001). There was a significant reduction in ovarian MPO activity in groups G4EAc2 and G5EAc100 (0.59Â0.21 vs 1.76Â0.31, p<0.05 and 0.65Â0.05 vs 1.76Â0.31p<0.001). MTF did not promote changes in oxidative or inflammatory markers. There was no change in blood glucose levels in any of the groups studied. Corpus luteum and follicular cysts number were not different in all groups. It is concluded that EAc2/100Hz treatments promote systemic and local protection on oxidative stress by increasing GSH concentrations and by reducing the inflammatory status in the ovary of healthy rats submitted to estrogenic stimulation.

O estresse crônico promove diversas alterações no funcionamento de um organismo. O aumento de glicocorticoides pode interferir no estado físico e psicológico de um individuo. Trabalhos recentes correlacionam estresse psicossocial crônico à redução do comprimento dos telômeros de determinadas células. E o estrógeno, além de ser um fator modulador da atividade do sistema de estresse, também pode interferir no comprimento dos telômeros. O objetivo desse trabalho foi verificar se a exposição crônica aos glicocorticóides promove alterações no comprimento dos telômeros de áreas encefálicas envolvidas no controle da atividade do eixo Hipotálamo-Hipófise-Adrenal (HPA) e em respostas comportamentais de ratas, e se o estrógeno pode modular essas alterações. Ratas Wistar ovariectomizadas foram tratadas com cipionato de estradiol (50 ou 100 µg/kg, s.c.) ou óleo, e submetidas à administração de corticosterona 20 mg/Kg ou veículo (salina isotônica 2% Tween 80, s.c.), durante 28 dias. No 25 º dia os animais foram submetidos ao teste do nado forçado, e no 27º dia, ao teste de labirinto em cruz elevado. No dia subsequente ao término do tratamento hormonal, os animais foram eutanasiados para coleta do sangue, cérebro e hipófise. O tratamento com cipionato de estradiol causou: aumento das concentrações plasmáticas de corticosterona e progesterona; redução da expressão de mRNA para CRH, AVP e POMC no PVN; um efeito ansiolítico a avaliado pelo teste do labirinto em cruz elevado; . um efeito depressivo indicado pelo teste de nado forçado; reduziu o tamanho dos na amígdala central e hipocampo dorsal, mas não no PVN. A corticosterona causou: redução da secreção de gonadotrofina; redução da expressão de RNA mensageiro para CRH e POMC e aumento para AVP no PVN; um efeito depressivo indicado pelo teste de nado forçado. O conjunto de resultados mostra que modificação na atividade do eixo HPA e a variação das concentrações plasmáticas de estrógeno podem provocar diversas alterações de ações hormonais, atividades comportamentais e de estrutura do DNA em áreas cerebrais.
Chronic stress promotes several changes in the functioning of an organism. Increased glucocorticoids may interfere with an individual\'s physical and psychological state. Recent works correlate chronic psychosocial stress to the reduction of the telomere length of certain cells. And estrogen, besides being a modulating factor of the activity of the stress system, can also interfere in the length of telomeres. The objective of this study was to verify if chronic exposure to glucocorticoids promotes changes in telomere length of encephalic areas involved in the control of hypothalamic-hypophysis-adrenal (HPA) axis activity and in rat behavioral responses, and whether estrogen can modulate these changes. Ovariectomized Wistar rats were treated with estradiol cypionate (50 or 100 ?g / kg, s.c.) or oil, and given 20 mg / kg corticosterone or vehicle (isotonic saline 2% Tween 80, s.c.) for 28 days. On the 25th day the animals were submitted to the forced swim test, and on the 27th day, the elevated plus maze test. On the day after the end of the hormonal treatment, the animals were euthanized for collection of blood, brain and pituitary gland. Treatment with estradiol cypionate caused: increased corticosterone and progesterone plasma concentrations; reduction of mRNA expression for CRH, AVP and POMC in PVN; an anxiolytic effect as assessed by the elevated plus maze test. A depressive effect indicated by the forced swim test; reduced size in the central amygdala and dorsal hippocampus, but not in PVN. Corticosterone caused: reduction of gonadotrophin secretion; reduction of mRNA expression for CRH and POMC and increase for AVP in PVN; a depressive effect indicated by the forced swim test. The set of results shows that changes in HPA axis activity and variation in plasma estrogen concentrations can lead to several changes in hormonal actions, behavioral activities and DNA structure in brain areas.

Evidências sugerem que as células da glia desempenham um papel importante na sinalização neuronal e na resposta inflamatória no Sistema Nervoso Central (SNC). Respostas inflamatórias crônicas, bem como a ativação da glia estão associadas com doenças neurodegenerativas, como Parkinson e Alzheimer. A inflamação crônica pode ser modulada por altas concentrações de espécies reativas de oxigênio (ERO) que potencializam esse quadro. O estrógeno (E2) é bem conhecido por suas ações neuroprotetoras que podem ser exercidas via receptores clássicos (ESR1, ESR2), não-classicos (GPER-1) ou ainda por sua ação antioxidante, proveniente da alta semelhança com as moléculas dos flavonóides. A ação do E2 no SNC é relevante uma vez que este hormônio está relacionado com a modulação da memória, neurogênese e plasticidade. Este trabalho tem como objetivo investigar o papel protetor do E2 em linhagem de células C6 de glioma de ratos em um modelo de estresse oxidativo que induz morte celular pela exposição a concentrações tóxicas de peróxido de hidrogênio (H2O2). Ensaios de PCR, Western Blot e de imunofluorescência confirmaram a presença e funcionalidade dos receptores ESR1, enquanto ensaios de PCR mostraram a presença do RNAm para o GPER-1 em células C6. Nossos resultados confirmaram que a H2O2 induz morte nas células C6 e o pré-tratamento com E2 (por 24 horas) e G1 (por 20 minutos) diminuiu a toxicidade da H2O2 de maneira dose-dependente, gerando aumento de viabilidade celular. Estes resultados destacam o envolvimento do E2 e seus receptores na prevenção do dano celular em células da glia. Além disso, eles também sugerem que o rápido efeito protetor do E2 parece estar associado com a sinalização rápida do E2 via GPER-1. Por Western blot e RT-PCR avaliamos a participação da via AKT-CREBBDNF frente aos tratamentos com E2, moduladores seletivos de estrógeno (SERMs) e G1, onde observamos que estes são capazes de modular a expressão da proteína AKT e os níveis de RNAm para BDNF.
Evidence suggests that glial cells play an important role in neuronal signaling and inflammatory responses in the central nervous system (CNS). Chronic inflammatory responses, as well as activation of glia, are associated with neurodegenerative disorders such as Parkinson´s and Alzheimer´s diseases. Chronic inflammation can be modulated by high concentrations of reactive oxygen species (ROS) that enhance this process. Estrogen (E2) is well known for its neuroprotective actions that can be performed via classical (ESR1, ESR2) and non-classical receptors (GPER-1) or by its antioxidant action due to its high similarity to flavonoids molecules. E2 action in the CNS is relevant as this hormone is associated to memory modulation, neurogenesis and plasticity. This work has as purpose to investigate the protective role of E2 in rat C6 glioma cell lines in a model of oxidative stress that induces cell death by exposure to toxic concentrations of hydrogen peroxide (H2O2). PCR, Western blot and immunofluorescence assays have confirmed the presence and functionality of the ESR1 receptor, while PCR assay has showed the presence of GPER-1 receptor mRNA in C6 cells. Our results confirmed that H2O2 induces cell death and pre-treatment with E2 (24 hours) and G1 (20 minutes) reduces H2O2 toxicity in a dose-dependent way, leading to increased cell viability. These results highlight the involvement of E2 and its receptors in preventing cell damage in glial cells. Moreover, they also suggest that the prompt E2 protective effect seems to be associated to the fast E2 signaling via GPER-1. We also evaluated the involvement of AKT-CREB-BDNF pathway when C6 cells were treated with E2, selective estrogen modulators (SERMs) and G1 by Western blot and RT-PCR assays, and we could notice that they can modulate the expression of AKT protein and BDNF RNAm levels.

Homocysteine (Hcy) is a sulfur containing amino acid and is a potent neurotoxin. It has been shown that elevated levels of Hcy, termed hyperhomocysteinemia, plays a role in the pathologies of Alzheimer’s disease (AD) and age-related cognitive decline. Hcy is a glutamate agonist, which causes in increase in Ca[superscript (2+)] influx via the activation of NMDA class of excitatory amino acid receptors, which results in neuronal cell death and apoptosis. Estrogen and progesterone are female hormones that are responsible for reproduction and maternal behaviour. However, in the last decade, it is evident that both female hormones have neuroprotective properties in many animal models of neurodegeneration. Collectively, both estrogen and progesterone reduce the consequences of the oxidative stress by enhancing the antioxidant defence mechanisms, reducing excitotoxicity by altering glutamate receptor activity and reducing the damage caused by lipid peroxidation. However, the mechanisms by which estrogen and progesterone provide such neuroprotection probably depend on the type and concentration of hormone present. Moreover, numerous studies have shown that hormone replacement therapy (HRT, estrogen and progestins) or estrogen-only replacement therapy (ERT) may prevent or delay the onset of AD and improve cognition for women with AD. Clinical trials have also shown that women taking HRT may modify the effects of Hcy levels on cognitive functioning. Oxidative stress increases in the aging brain and thus has a powerful effect on enhanced susceptibility to neurodegenerative disease. The detection and measurement of lipid peroxidation and superoxide anion radicals in the brain tissue supports the involvement of free radical reactions in neurotoxicity and in neurodegenerative disorders. The hippocampus is an important region of the brain responsible for the formation of memory. However, agents that induce stress in this area have harmful effects and could lead to dementia. This study aims to investigate and clarify the neuroprotective effects of estrogen and progesterone, using Hcy-induced neurodegenerative models. The initial studies demonstrate that estrogen and progesterone have the ability to scavenge potent free radicals. Histological studies undertaken reveal that both estrogen and progesterone protect against Hcy-induced neuronal cell death. In addition, immunohistochemical investigations show that Hcy-induced apoptosis in the hippocampus can be inhibited by both estrogen and progesterone. However, estrogen also acts at the NMDA receptor as an agonist, while progesterone blocks at the NMDA receptor. These mechanisms reduce the ability of Hcy to cause damage to neurons, since Hcy-induced neurotoxicity is dependent on the overstimulation of the NMDA receptor. SOD and GPx are important enzymatic antioxidants which can react with ROS and neutralize them before these inflict damage in the brain. Hcy can increase oxidative stress by inhibiting expression and function of these antioxidants. However, it has been shown that the antioxidant abilities of both estrogen and progesterone can up-regulate the activities of SOD and GPx. These results provide further evidence that estrogen and progesterone act as antioxidants and are free radical scavengers. The discovery of neuroprotective agents is becoming important as accumulating evidence indicates the protective role of both estrogen and progesterone in Hcy-induced neurodegeneration. Thus further work in clinical trials is needed to examine whether reducing Hcy levels with HRT can become the treatment of neurodegenerative disorders, such as Alzheimer’s disease.

This chapter focuses primarily on the influence of female sex as a risk factor for posttraumatic stress disorder (PTSD). Prevalence rates suggest that women are especially vulnerable to developing PTSD. Despite changes in diagnostic criteria and examination across varied populations, the prevalence of PTSD remains consistently twice as high in women as men. This chapter examines sex differences in both incidence and presentation of PTSD. It then moves to a discussion of the neurobiological factors of PTSD in women, further examining stress and fear regulation mechanisms and the circuitry that may underlie the disproportionate vulnerability to PTSD development in women. The influence of gonadal hormones on PTSD symptomology is also explored in this chapter with a focus on estrogen and progesterone.

Epidemiologic and clinical findings demonstrate that women are at increased risk for chronic pain, experience greater pain-related distress, and show heightened sensitivity for pain compared to men. There are differences in analgesic responses to pain and to both opioid and non-opioid medications as well as for endogenous analgesic processes. Many stress-related disorders, such as fibromyalgia and chronic pain, are more prevalent in women. Studies of experimentally induced pain show that women exhibit greater pain sensitivity, enhanced pain facilitation, and reduced pain inhibition compared to men. Mechanisms that implicated in the underlying sex differences include biological involvement of estrogen and progesterone versus testosterone. Sex-related differences in pain may also reflect differences in the endogenous opioid system. Other mechanisms include steroid action differences in adulthood, modulation of various biological systems such as the cardiovascular and inflammatory pathways, and sociocultural differences

In 2010, alcoholic beverage consumption caused an estimated 3.3 million deaths worldwide, and contributed to injuries, violence, liver cirrhosis, social disruption and at least seven different types of cancer. The International Agency for Research on Cancer (IARC) classifies exposure to both ethanol in alcoholic beverages and acetaldehyde, the primary metabolite of ethanol, as carcinogenic to humans (Group 1) based on “sufficient” evidence that alcoholic beverage consumption is causally related to cancers of the oral cavity, pharynx, larynx, esophagus, liver, colorectum and female breast. The biologic mechanisms by which alcohol and its primary metabolite acetaldehyde affect cancer risk appear to vary across anatomic sites. Broadly, these mechanisms involve DNA and protein damage from acetaldehyde and oxidative stress, nutritional malabsorption and metabolic effects, and for breast cancer, increased estrogen levels. The World Health Organization has increased global surveillance of alcohol consumption and encourages national efforts to apply evidence-based policies to reduce consumption.

As best-selling author John Gray pointed out, men are from Mars and women are from Venus. There are obvious differences between women and men in anatomy, physiology, hormones, and metabolism. So why do most running books take a one-size-fits-all approach to training? Finally, here's one that doesn't. Running for Women provides comprehensive information on training female runners based on their cardiovascular, hormonal, metabolic, muscular, and anatomical characteristics. In this authoritative guide, authors Jason Karp and Carolyn Smith answer the questions and tackle the topics women need to know: • The impact of the menstrual cycle on hydration, body temperature, metabolism, and muscle function • The most effective workouts for endurance, speed and strength, lactate threshold, and VO2max • How and when to train during the menstrual cycle, pregnancy, and menopause • Preventing knee injuries, stress fractures, and other common running-related injuries • Avoiding the risks of the female athlete triad disordered eating, osteoporosis, and menstrual irregularities • How to use sex differences to your advantage Based on the latest research on estrogen, metabolism, and other sex-specific performance factors, Running for Women will change the way you fuel, train, and compete. If you are serious about running, this is one guide you must own.

Menopause refers to a point in time that follows 1 year after complete cessation of menstruation. Menopausal transition and years spent in the post-menopausal state bring with them issues related to quality of life and disease prevention and manegement. With the onset of menopause and due to the lacking effect of estrogen, basal metabolism of the female body decreases significantly. During perimenopause and menopause, many lifestyle factors can reduce the risk of developing diseases (cardiovascular disease, insulin resistance, type 2 diabetes, osteoporosis and tumors) and symptoms specific to this period with appropriate nutritional diets. The management and prevention of osteoporosis and related low energy fractures start with a correct lifestyle and proper nutrition. Calcium is the main actor in bone health. It is the principal component of the mineralized bone matrix where more than 99% of the total body calcium is contained; its key role in maintaining bone health throughout life has been recognized by many studies. Alterations in lipid metabolism and excessive adipose tissue play a key role in the synthesis of excess fatty acids, adipocytokines, proinflammatory cytokines, and reactive oxygen species, which cause lipid peroxidation and result in the development of insulin resistance, abdominal adiposity, and dyslipidemia. Oxidative stres is defined as a derangement in the balance between oxidants and antioxidants, which damages biological structures and contributes to disease progression. As menopause is associated with altered lipid levels and increased risk of metabolic disorders, including CVD, postmenopausal women must consume recommended diets and beneficial foods.

In recent years, there has been a growing interest in the potential health benefits of phytoestrogens, a diverse group of naturally occurring compounds found in plants. These compounds, with structural similarities to estrogen, are found in foods such as soybeans, flaxseeds and sesame seeds, and are studied for their roles in modulating hormonal activity and antioxidant properties. Their estrogen-like functions make them particularly interesting in managing conditions exacerbated by hormonal imbalances, such as type 2 diabetes, obesity, cardiovascular diseases, and osteoporosis. Phytoestrogens enhance insulin sensitivity and glucose metabolism, while their anti-oxidant properties neutralize free radicals and inhibit lipid peroxidation. They also influence fat metabolism and reduce adipogenesis, addressing oxidative stress and inflammation. Their estrogenic effects improve bone mineral density and reduce fracture risks, particularly in postmenopausal women, highlighting their broad potential in metabolic disease management. This growing body of research suggests that phytoestrogens, due to their unique properties and diverse mechanisms of action, could be a valuable addition to dietary and therapeutic strategies in the prevention and management of various metabolic diseases. This chapter delves into the multifaceted roles of phytoestrogens in metabolic disorders, with a special focus on their antioxidant properties.

Hypoxic–ischemic brain injury is a number one cause of long-term neurologic disability and death worldwide. This public health burden is mainly characterized by a decrease in oxygen concentration and blood flow to the tissues, which lead to an inefficient supply of nutrients to the brain. This condition induces cell death by energy depletion and increases free radical generation and inflammation. Hypoxic–ischemic brain injury may occur in ischemic-stroke and over perinatal asphyxia, being both leading causes of morbidity in adults and children, respectively. Currently, there are no effective pharmaceutical strategies to prevent the triggering of secondary injury cascades, including oxidative stress and metabolic dysfunction. Neuroactive steroids like selective estrogen receptor modulators, SERMs, and selective tissue estrogenic activity regulators, STEARs, exert several neuroprotective effects. These encompass mitochondrial survival, a decrease in reactive oxygen species, and maintenance of cell viability, among others. In this context, these neurosteroids constitute promising molecules, which could modify brain response to injury. Here we show an updated overview of the underlying mechanisms of hypoxic–ischemic brain injury. We also highlight the neuroprotective effects of neurosteroids and their future directions.

This section of Nutraceuticals-I focuses on the detailed study of specific nutraceuticals and functional foods, including Spirulina, Soybean, and Ginseng. Spirulina, a blue-green algae, is rich in proteins, vitamins, and antioxidants, with phycocyanin as its key marker compound, offering anti-inflammatory and immune-boosting benefits. Soybean, a leguminous crop, is well-known for its high isoflavone content, particularly genistein and daidzein, which exhibit estrogenic activity and contribute to cardiovascular health and osteoporosis prevention. Ginseng, a widely used herbal remedy, contains ginsenosides as its primary bioactive components, which are known for their adaptogenic properties, enhancing energy levels, reducing stress, and improving cognitive function. This study underscores the chemical nature of these compounds, their roles in traditional and modern medicine, and their broader health benefits, making them significant contributors to the field of nutraceuticals and functional foods.

Part IV of this book briefly integrates lessons learned among the many chapters and discusses paths forward for future research in both animals and humans. Suggested future directions for animal research include continued efforts to uncover molecular, cell-specific, and circuit-level mechanisms through which estrogens regulate memory, increased attention to glia, de novo estrogen synthesis, interactions between neuromodulators, sex differences, hormonal changes across the lifespan, multiple brain regions, multiple forms of memory, and improving our models of menopause and estrogen therapy. Future clinical work would benefit better understanding the role of various estrogens in regulating cognition and mental illness in humans throughout the lifespan. In particular, many questions remain to be answered for menopausal women, including how reproductive history, menopausal estrogen loss, genetics, diet, stress, metabolic alterations, cardiovascular disease, and inflammation interact to influence memory and mood dysfunction. Addressing these issues will provide sorely needed insights into estrogen regulation of memory.

Curculigo orchioides Gaertn. is a rare herb belonging to the family Hypoxidaceae, popularly known as “Kali Musli” in India, “Sam Cau”, “Tien Mao” in Vietnam, “Xian Mao” in China. This species is native and widely distributed in Asian countries such as India, Nepal, Pakistan, South China, Laos, Vietnam, Myanmar, and the Philippines. C. orchioides contains several classes of chemicals, including saponins, alkaloids, flavonoids, phytosterols, steroids, free reducing sugars starch, proteins, resins, tannins, mucilage, fats, and inorganic compounds. Rhizoma Curculiginis is used in traditional medicine remedies in various countries for the treatment of a range of ailments, including impotency, aphrodisiacs, tonics, jaundice, and skin conditions. The scientific evidence indicates its aphrodisiac, spermatogenic, estrogenic, immunomodulatory, antioxidant, anti-inflammatory, antiosteoporosis, antidepressant, hepatoprotective, nephroprotective, antidiabetic, antimicrobial. Antiasthmatic, antistress, anticancer, antigout, antihypertensive, antimalarial, and cardiovascular activities. As traditional herbal medicine, C. orchioides has been investigated for its pharmacological activity against diabetes, fungi, bacteria, inflammation, osteoporosis, oxidative stress, cancer, and neurodegeneration. Findings of bioactive compounds and the biological effects of the extract of C. orchioides provide scientific support for the folk use of this plant in the traditional, unvalidated herbal drugs as aphrodisiac and rejuvenating tonics.

Abstract A theoretical model has been developed based on fuzzy logic control to predict bony response to mechanical load and estrogen. The results show good agreement with the experimental findings, which suggests that bone may be regulated by simple remodeling rules, similar to those used in the fuzzy logic control.