Roles of estrogen receptor-alpha in mediating life span: the hypothalamic deregulation hypothesis

Gouw, Arvin M.; Efe, Gizem; Barakat, Rita; Preecha, Andrew; Mehdizadeh, Morvarid; Garan, Steven A.; Brooks, George A.

doi:10.1152/physiolgenomics.00073.2016

Cited by 8 publications

(5 citation statements)

References 56 publications

(120 reference statements)

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“…Studies from humans and rodent models indicate that, among the three ERs, ERα may be a key player in preserving health in advanced age. Indeed, ERα contributes to maintain biological functions such as cardiovascular, metabolic, cognitive, hypothalamic, and limbic functions, even under conditions of low estrogen levels [27,28]. This might be due to the higher affinity of ERα with E2, compared to the affinity with E2 of the other ER subtypes [29,30].…”

Section: Introductionmentioning

confidence: 99%

Differential ESR1 Promoter Methylation in the Peripheral Blood—Findings from the Women 40+ Healthy Aging Study

Gardini

Chen

Fiacco

et al. 2020

IJMS

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Background Estrogen receptor α (ERα) contributes to maintaining biological processes preserving health during aging. DNA methylation changes of ERα gene (ESR1) were established as playing a direct role in the regulation of ERα levels. In this study, we hypothesized decreased DNA methylation of ESR1 associated with postmenopause, lower estradiol (E2) levels, and increased age among healthy middle-aged and older women. Methods We assessed DNA methylation of ESR1 promoter region from dried blood spots (DBSs) and E2 from saliva samples in 130 healthy women aged 40–73 years. Results We found that postmenopause and lower E2 levels were associated with lower DNA methylation of a distal regulatory region, but not with DNA methylation of proximal promoters. Conclusion Our results indicate that decreased methylation of ESR1 cytosine-phosphate-guanine island (CpGI) shore may be associated with conditions of lower E2 in older healthy women.

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Section: Introductionmentioning

confidence: 99%

Differential ESR1 Promoter Methylation in the Peripheral Blood—Findings from the Women 40+ Healthy Aging Study

Gardini

Chen

Fiacco

et al. 2020

IJMS

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“…Recently, intermittent fasting or fasting/refeeding has also shown to extend lifespan and have beneficial health effects as compared to ad libitum food consumption, 3 , 13 , 14 as it enhances cardiovascular function and improves several risk factors for cardiovascular diseases. 15 , 16 This dietary approach also implies a protective effect against oxidative stress, lower rates of kidney disease, 17 prolongation of reproductive function, 18 and leads to the normalization of resting energy expenditure and protein synthesis recuperation, but can cause many metabolic disturbances. 19 , 20…”

Section: Introductionmentioning

confidence: 99%

Fasting/Refeeding Cycles Prevent Myocardial Dysfunction and Morphology Damage in the Spontaneously Hypertensive Rats

Pinotti

Matias

Sugizaki

et al. 2018

Arquivos Brasileiros De Cardiologia

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BackgroundCaloric restriction is known to impair the cardiac function and morphology in hypertrophied hearts of spontaneously hypertensive rats (SHR); however, the influence of fasting/refeeding (RF) is unknown.ObjectiveTo investigate the fasting/refeeding approach on myocardial remodeling and function. In addition, the current study was designed to bring information regarding the mechanisms underlying the participation of Ca2+ handling and β-adrenergic system.MethodsSixty-day-old male SHR rats were submitted to food ad libitum (C), 50% food restriction (R50) or RF cycles for 90 days. Cardiac remodeling was assessed by ultrastructure analysis and isolated papillary muscle function. The level of significance considered was 5% (α = 0.05).ResultsThe RF rats presented lower cardiac atrophy than R50 in relation to C rats. The C rats increased weight gain, R50 maintained their initial body weight and RF rats increased and decreased weight during RF. The RF did not cause functional impairment because the isotonic and isometric parameters showed similar behavior to those of C. The isotonic and isometric cardiac parameters were significantly elevated in RF rats compared to R50 rats. In addition, the R50 rats had cardiac damage in relation to C for isotonic and isometric variables. While the R50 rats showed focal changes in many muscle fibers, the RF rats displayed mild alterations, such as loss or disorganization of myofibrils.ConclusionFasting/refeeding promotes cardiac beneficial effects and attenuates myocardial injury caused by caloric restriction in SHR rats, contributing to reduce the cardiovascular risk profile and morphological injuries. Furthermore, RF promotes mild improvement in Ca2+ handling and β-adrenergic system.

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“…ERα and ERβ are expressed in the brain of both male and female rodents. ERα expression in the hypothalamus contributes to learning and memory functions [43]. We have investigated the effect BPA exposure on ERα and oxtr expression in the hypothalamus of mice with or without OVA immunization.…”

Section: Resultsmentioning

confidence: 99%

Memory Function, Neurological, and Immunological Biomarkers in Allergic Asthmatic Mice Intratracheally Exposed to Bisphenol A

Win-Shwe

Yanagisawa

Koike

et al. 2019

IJERPH

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Bisphenol A (BPA) is a major constituent of plastic products, including epoxy resin containers, mobile phones, dental sealants, as well as electronic and medical equipment. BPA is recognized as an endocrine system-disrupting chemical which has toxic effects on the brain and reproductive system. However, little is known about the effects of co-exposure of BPA with allergens on the memory function and neurological as well as immunological biomarker levels. In this study, we examined the effects of intratracheal instillation of BPA on the memory function and neuroimmune biomarker levels using a mouse model of allergic asthma. Male C3H/HeJ Jcl mice were given three doses of BPA (0.0625 pmol, 1.25 pmol, and 25 pmol BPA/animal) intratracheally once a week, and ovalbumin (OVA) intratracheally every other week from 5 to 11 weeks old. At 11 weeks of age, a novel object recognition test was conducted after the final administration of OVA, and the hippocampi and hypothalami of the animals were collected after 24 h. The expression levels of the memory function-related genes N-methyl-D-aspartate (NMDA) receptor subunits, inflammatory cytokines, microglia markers, estrogen receptor-alpha, and oxytocin receptor were examined by real-time RT-PCR (real-time reverse transcription polymerase chain reaction) and immunohistochemical methods. Impairment of the novel object recognition ability was observed in the high-dose BPA-exposed mice with allergic asthma. In addition, the allergic asthmatic mice also showed downregulation of neurological biomarkers, such as NMDA receptor subunit NR2B in the hippocampus but no significant effect on immunological biomarkers in the hypothalamus. These findings suggest that exposure to high-dose BPA triggered impairment of memory function in the allergic asthmatic mice. This is the first study to show that, in the presence of allergens, exposure to high-dose BPA may affect memory by modulating the memory function-related genes in the hippocampus.

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Roles of estrogen receptor-alpha in mediating life span: the hypothalamic deregulation hypothesis

Cited by 8 publications

References 56 publications

Differential ESR1 Promoter Methylation in the Peripheral Blood—Findings from the Women 40+ Healthy Aging Study

Differential ESR1 Promoter Methylation in the Peripheral Blood—Findings from the Women 40+ Healthy Aging Study

Fasting/Refeeding Cycles Prevent Myocardial Dysfunction and Morphology Damage in the Spontaneously Hypertensive Rats

Memory Function, Neurological, and Immunological Biomarkers in Allergic Asthmatic Mice Intratracheally Exposed to Bisphenol A

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