scholarly journals Estrogen modulation of pain perception with a novel 17β-estradiol pretreatment regime in ovariectomized rats

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenxin Zhang ◽  
Hui Wu ◽  
Qi Xu ◽  
Sheng Chen ◽  
Lihong Sun ◽  
...  
Keyword(s):  
Pain Perception ◽  
Pain Modulation ◽  
Mechanical Hyperalgesia ◽  
Ovariectomized Rats ◽  
Estrogen Replacement ◽  
Hormone Substitution ◽  
Independent Manner ◽  
Stable Period ◽  
Ovx Rats ◽  
Estrogen Depletion

AbstractEstrogen plays substantial roles in pain modulation; however, studies concerning sex hormones and nociception often yield confusing results. The discrepancy could be a result of lack of consensus to regard estrogen as a variable when working with animal models; thus, the influence of hormones’ fluctuations on nociception has continually been neglected. In the present study, we designed a novel hormone substitution model to aid us to evaluate the effects of estrogen’s long-term alterations on ovariectomy (OVX)-induced mechanical hyperalgesia and the expression of estrogen receptors(ERs). OVX rats were implanted with slow-release estrogen pellets at differently arranged time points and doses, such that a gradual elevation or decrease of serum estrogen levels following a relatively stable period of estrogen replacement was achieved in rats. Our results demonstrated that gradual estrogen depletion rather than elevation following the stable period of estrogen substitution in OVX rats alleviated OVX-induced mechanical hyperalgesia in a dose-independent manner, and the opposite estrogen increase or decrease paradigms differently regulate the expression of spinal ERs. Specifically, in rats rendered to continuously increased serum estrogen, the early phase estrogen-induced anti-nociception effect in OVX rats was eliminated, which was accompanied by an over-activation of ERα and a strong depression of ERβ, while in the OVX rats subject to gradual decrease of estrogen replacement, both ERα and ERβ increased modestly compared with the OVX group. Thus, the present study demonstrated that estrogen increase or decrease modulate nociception differently through change of spinal ERs.

Effects of resistance training and estrogen replacement on adipose tissue inflammation in ovariectomized rats

2017 ◽  
Vol 42 (6) ◽  
pp. 605-612 ◽  
Author(s):  
Maria Fernanda Cury Rodrigues ◽  
Fabiano Candido Ferreira ◽  
Natália Santanielo Silva-Magosso ◽  
Marina Rodrigues Barbosa ◽  
Markus Vinicius Campos Souza ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Resistance Training ◽  
Ovariectomized Rats ◽  
Low Grade ◽  
Estrogen Replacement ◽  
Expression Levels ◽  
Inflammatory Status ◽  
Ovx Rats ◽  
Tnf Α ◽  
Gene And Protein Expression

Estrogen deficiency is directly related to central obesity and low-grade inflammation. Hormonal replacement and exercise training are both able to decrease fat accumulation and inflammation in postmenopausal women. However, the efficiency of resistance training (RT) and estrogen replacement (ER) in minimizing adiposity and inflammation in the visceral adipose tissue (VAT) of ovariectomized (OVX) rats has not yet been elucidated. In this study, Sprague–Dawley rats were divided into the following 6 groups: sham-operated sedentary (Sham-Sed), OVX-Sed, Sham-RT, OVX-RT, OVX-Sed-ER, and OVX-RT-ER groups. ER was performed by implanting silastic capsules containing 17β-estradiol. For RT, the animals were required to climb a 1.1-m vertical ladder with conical flasks containing weights attached to their tails for 12 weeks. Histological analyses were used to evaluate morphological changes. Gene expression levels were determined by quantitative real-time reverse transcriptase polymerase chain reaction, and protein concentrations were determined using Multiplex/Luminex assays. Ovariectomy increased the body mass (BM), adipocyte area, and inflammation in the VAT, the latter of which was indicated by reduced interleukin-10 (48%) and increased tumor necrosis factor (TNF)-α concentration (∼3%). RT efficiently decreased BM, adipocyte area, and inflammation in the OVX groups. The combination of RT and ER decreased BM (19%) and the TNF-α concentration (18%) and increased the gene and protein expression levels of adiponectin (173% and 18%). These results indicate that RT and the combination of RT and ER are efficient strategies for reducing the BM and improving the inflammatory status of OVX rats.

scholarly journals Estrogen Inhibits Colon Polyp Formation by Reducing Angiogenesis in a Carcinogen-Induced Rat Model

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jia Yang ◽  
Li-juan Xiong ◽  
Fei Xu ◽  
Xiang Zhao ◽  
Bo Liu ◽  
...  
Keyword(s):  
Rat Model ◽  
Colon Polyp ◽  
Ovariectomized Rats ◽  
Nuclear Antigen ◽  
Control Group ◽  
Colon Polyps ◽  
Estrogen Replacement ◽  
Polyp Formation ◽  
Ovx Rats ◽  
Proliferating Cell

Objective.To study the effects of estrogen on colon polyp formation, proliferation, and angiogenesis on a rat model of colon cancer induced by dimethylhydrazine (DMH).Methods.Thirty-six female ovariectomized (OVX) rats were randomly divided into 3 groups: (I) control group (administrated with vehicles weekly), (II) DMH group (administrated with DMH weekly), and (III) DMH + E2group (administrated with DMH and 17β-estradiol weekly). The incidence, volumes, and multiplicity of colon polyps in each group were evaluated. The microvessel density (MVD), the expressions of Proliferating Cell Nuclear Antigen (PCNA), and the expressions of HIF-1αand VEGF in polyps were detected in each group.Results.Estrogen reduced the multiplicity, volumes, and the PCNA expressions of DMH-induced colon polyps. The MVD in DMH + E2group was significantly lower than that in DMH group. Estrogen treatment decreased the HIF-1αand VEGF expressions at both mRNA and protein level.Conclusion.Estrogen replacement was protective for ovariectomized rats from DMH-induced carcinogenesis, and one of the mechanisms for this was due to estrogen’s inhibitive effects on blood vessel formation by downregulating VEGF and HIF-1αexpressions.

scholarly journals Estrogen replacement restores flow-induced vasodilation in coronary arterioles of aged and ovariectomized rats

2009 ◽  
Vol 297 (6) ◽  
pp. R1713-R1723 ◽  
Author(s):  
Amanda J. LeBlanc ◽  
Rafael Reyes ◽  
Lori S. Kang ◽  
Robert A. Dailey ◽  
John N. Stallone ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ovarian Hormones ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Estrogen Replacement ◽  
Cvd Risk ◽  
Young Females ◽  
Ovx Rats ◽  
Coronary Arterioles ◽  
Reduced Flow

The risk for cardiovascular disease (CVD) increases with advancing age; however, the age at which CVD risk increases significantly is delayed by more than a decade in women compared with men. This cardioprotection, which women experience until menopause, is presumably due to the presence of ovarian hormones, in particular, estrogen. The purpose of this study was to determine how age and ovarian hormones affect flow-induced vasodilation in the coronary resistance vasculature. Coronary arterioles were isolated from young (6 mo), middle-aged (14 mo), and old (24 mo) intact, ovariectomized (OVX), and ovariectomized + estrogen replaced (OVE) female Fischer-344 rats to assess flow-induced vasodilation. Advancing age impaired flow-induced dilation of coronary arterioles (young: 50 ± 4 vs. old: 34 ± 6; % relaxation). Ovariectomy reduced flow-induced dilation in arterioles from young females, and estrogen replacement restored vasodilation to flow. In aged females, flow-induced vasodilation of arterioles was unaltered by OVX; however, estrogen replacement improved flow-induced dilation by ∼160%. The contribution of nitric oxide (NO) to flow-induced dilation, assessed by nitric oxide synthase (NOS) inhibition with NG-nitro-l-arginine methyl ester (l-NAME), declined with age. l-NAME did not alter flow-induced vasodilation in arterioles from OVX rats, regardless of age. In contrast, l-NAME reduced flow-induced vasodilation of arterioles from estrogen-replaced rats at all ages. These findings indicate that the age-induced decline of flow-induced, NO-mediated dilation in coronary arterioles of female rats is related, in part, to a loss of ovarian estrogen, and estrogen supplementation can improve flow-induced dilation, even at an advanced age.

Abstract 086: Estrogen Replacement Downregulates Cardiac Angiotensin II in an ACE-independent Manner in Oophorectomized mRen2.Lewis Rats

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Hao Wang ◽  
Zhuo Zhao ◽  
Jewell Jessup ◽  
Marina Lin ◽  
Lindsay MacNamara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Sham Operation ◽  
Dependent Manner ◽  
Ang Ii ◽  
Estrogen Replacement ◽  
Bilateral Oophorectomy ◽  
Independent Manner ◽  
Lewis Rats ◽  
Ovx Rats

The cardioprotective effects of estrogen are well recognized, but the mechanisms remain poorly understood. Accumulating evidence suggests that the local cardiac renin-angiotensin system (RAS) is involved in the development and progression of left ventricle (LV) remodeling and diastolic dysfunction (LVDD). Estrogen attenuates the effects of an activated circulating RAS, however, its role in regulating the cardiac RAS is unclear. We hypothesized that estrogen replacement limits the development of the LVDD phenotype after ovarian hormone loss by shifting the RAS from the pro-fibrotic angiotensin II (Ang II)/ Ang II type 1 receptor (AT1R)/converting enzyme (ACE) and aldosterone pathway to the anti-fibrotic, Ang-(1-7)/Mas/ACE2 pathway. Bilateral oophorectomy (OVX; n=17) or sham-operation (Sham; n=13) was performed in 4-week-old, female mRen2.Lewis rats. At 11 weeks of age, after the development of exacerbated hypertension, the rats were randomized and received either 17 β-estradiol (E2, 36 μg/pellet, 60 day release, n=8) or vehicle (OVX-V, n=9) for 4 weeks. E2 treatment attenuated the adverse effects of estrogen loss on tissue Doppler-derived diastolic indices, e′ and E/e′, without changing blood pressure. E2 treatment minimized the rise in circulating Ang II and aldosterone, following OVX. Chronic E2 also attenuated OVX-associated increases in cardiac Ang II, Ang-(1-7), and chymase expression, and in mast cell number as determined by real-time PCR, western blot, and immunohistochemical analyses. Neither OVX nor OVX+E2 altered cardiac expression of AT1R, or gene expression and activity of cardiac ACE. E2 treatment in OVX rats significantly decreased gene expression of MMP-9, ACE2, and Ang-(1-7) mas receptor, in comparison to sham-operated, intact and OVX littermates. In conclusion, E2 treatment inhibits upsurges in cardiac Ang II expression in the OVX-mRen2 rat, possibly in a non-ACE-dependent manner. Further studies are warranted to determine whether an E2-mediated reduction in cardiac chymase directly contributes to this response in OVX rats.

NO mediates effects of estrogen on central regulation of blood pressure in restrained, ovariectomized rats

2003 ◽  
Vol 285 (4) ◽  
pp. R842-R849 ◽  
Author(s):  
Anton Cherney ◽  
Heather Edgell ◽  
Teresa L. Krukoff
Keyword(s):  
Arterial Pressure ◽  
Psychological Stress ◽  
Cardiovascular Responses ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
No Production ◽  
Estrogen Replacement ◽  
Ovx Rats ◽  
Intracerebroventricular Injections ◽  
The Brain

We tested the hypotheses that estrogen replacement in ovariectomized (OVX) rats attenuates cardiovascular responses to psychological stress and that nitric oxide (NO) in the brain mediates these effects. Female rats were OVX; one group received 17β-estradiol (OVX-E) for 11-12 days and the other received vehicle (OVX-V). Seven days after OVX, OVX-E and OVX-V rats were chronically instrumented for arterial pressure measurements and intracerebroventricular injections. Later (4-5 days), OVX-E and OVX-V rats received intracerebroventricular injections of NG-nitro-l-arginine (88 μg/kg), an inhibitor of constitutive NO production, or vehicle. Mean arterial pressure (MAP) and heart rate responses were then measured in conscious rats exposed to two cycles of 1-h restraint/1-h rest. We show that MAP responses in restrained OVX-E rats were attenuated both during restraint and during rest. Although inhibition of NO production in the brain had no effect on MAP responses to restraint in OVX-V rats, it augmented responses in restrained OVX-E rats, especially during periods of rest, so that MAPs in restrained OVX-E and OVX-V rats were indistinguishable. Finally, NO levels in hypothalami and brain stems were elevated in restrained OVX-E, but not OVX-V, rats compared with their respective unrestrained controls. These results show that estrogen replacement in OVX rats reduces arterial pressure responses to psychological stress and that these effects are mediated, at least in part, by NO.

Dexfenfluramine: action with estradiol on food intake and body weight in ovariectomized rats

1990 ◽  
Vol 258 (1) ◽  
pp. R211-R215 ◽  
Author(s):  
A. M. Souquet ◽  
N. E. Rowland
Keyword(s):  
Weight Loss ◽  
Weight Gain ◽  
Food Intake ◽  
Chronic Administration ◽  
Inhibitory Effect ◽  
Normal Weight ◽  
Ovariectomized Rats ◽  
Estrogen Replacement ◽  
Ovx Rats ◽  
Adipose Tissue Lipoprotein Lipase

Previous work from this laboratory has shown that chronic administration of dexfenfluramine (DF) caused substantial weight loss in rats that were overweight 3-4 mo after ovariectomy (OVX), but not in OVX rats that were of normal weight, as a result of estrogen replacement. The present study was conducted to determine whether the enhanced weight loss in the former group is because of either overweight per se or an inhibitory effect of estrogen on DF. Starting either 0, 6, or 14 wk after OVX, when weight gain was zero, moderate, or near maximal, respectively, rats received a 12-day regimen of either estradiol or the oil vehicle and either DF (3 mg.kg-1.day-1 by osmotic minipump) or no drug. DF had no effect on either food intake or weight gain of groups treated during 0-2 wk after OVX but had significant anorectic and weight loss actions in groups treated 6-8 and 14-16 wk after OVX. Estrogen had a similar effect at all three times and in the 14-wk group produced an effect that was additive with that of DF. Measures of plasma glucose and triglycerides and adipose tissue lipoprotein lipase activity did not correlate with the effectiveness of the drug to promote weight loss.

scholarly journals Estrogen Replacement Reduces Oxidative Stress in the Rostral Ventrolateral Medulla of Ovariectomized Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Fan Hao ◽  
Ying Gu ◽  
Xing Tan ◽  
Yu Deng ◽  
Zhao-Tang Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Rostral Ventrolateral Medulla ◽  
Sympathetic Tone ◽  
Ovariectomized Rats ◽  
Ventrolateral Medulla ◽  
Sympathetic Outflow ◽  
Protective Effects ◽  
Estrogen Replacement ◽  
Ovx Rats

Cardiovascular disease prevalence rises rapidly after menopause, which is believed to be derived from the loss of estrogen. It is reported that sympathetic tone is increased in postmenopause. The high level of oxidative stress in the rostral ventrolateral medulla (RVLM) contributes to increased sympathetic outflow. The focus of this study was to determine if estrogen replacement reduces oxidative stress in the RVLM and sympathetic outflow in the ovariectomized (OVX) rats. The data of this study showed that OVX rat increased oxidative stress in the RVLM and sympathetic tone; estrogen replacement improved cardiovascular functions but also reduced the level of oxidative stress in the RVLM. These findings suggest that estrogen replacement decreases blood pressure and sympathoexcitation in the OVX rats, which may be associated with suppression in oxidative stress in the RVLM through downregulation of protein expression of NADPHase (NOX4) and upregulation of protein expression of SOD1. The data from this study is beneficial for our understanding of the mechanism of estrogen exerting cardiovascular protective effects on postmenopause.

Altered Ca2+ handling by ryanodine receptor and Na+-Ca2+ exchange in the heart from ovariectomized rats: role of protein kinase A

2007 ◽  
Vol 292 (5) ◽  
pp. C1625-C1635 ◽  
Author(s):  
Gennadi M. Kravtsov ◽  
Kenneth W. L. Kam ◽  
Jing Liu ◽  
Song Wu ◽  
Tak Ming Wong
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Ryanodine Receptor ◽  
Contractile Function ◽  
Left Ventricular ◽  
Ovariectomized Rats ◽  
Estrogen Replacement ◽  
Ovx Rats ◽  
Developed Pressure ◽  
Kinase A

Our previous study has demonstrated that ovariectomy (Ovx) significantly increased the left ventricular developed pressure (LVDP) and the maximal rate of developed pressure over time (±dP/d tmax) in the isolated perfused rat heart and the effects were reversed by female sex hormone replacement. In the present investigation, we studied the effects of Ovx for 6 wk on Ca2+ homeostasis that determines the contractile function. Particular emphasis was given to Ca2+ handling by ryanodine receptor (RyR) and Na+-Ca2+ exchange (NCX). 45Ca2+ fluxes via the RyR, NCX, and Ca2+-ATPase (SERCA) were compared with their expression in myocytes from Ovx rats with and without estrogen replacement. Furthermore, we correlated the handling of Ca2+ by these Ca2+ handling proteins with the overall Ca2+ homeostasis by determining the Ca2+ transients induced by electrical stimulation and caffeine, which reveals the dynamic changes of cytosolic Ca2+ concentration ([Ca2+]i) in the heart. In addition, we determined the expression and contribution of protein kinase A (PKA) to the regulation of the aforementioned Ca2+ handling proteins in Ovx rats. It was found that after Ovx there were 1) increased Ca2+ fluxes via RyR and NCX, which were reversed not only by estrogen replacement, but more importantly by blockade of PKA; 2) an increased expression of PKA; and 3) no increase in expression of NCX and SERCA. We suggest that hyperactivities of RyR and NCX are a result of upregulation of PKA. The increased release of Ca2+ through RyR and removal of Ca2+ by NCX are believed to be responsible for the greater contractility and faster relaxation after Ovx.

scholarly journals 17β-Estradiol Exacerbated Experimental Occlusal Interference-Induced Chronic Masseter Hyperalgesia by Increasing the Neuronal Excitability and TRPV1 Function of Trigeminal Ganglion in Ovariectomized Rats

2021 ◽  
Vol 22 (13) ◽  
pp. 6945
Author(s):  
Yun Liu ◽  
Xiao-Xiang Xu ◽  
Ye Cao ◽  
Si-Yi Mo ◽  
Shan-Shan Bai ◽  
...  
Keyword(s):  
Trigeminal Ganglion ◽  
Transient Receptor Potential ◽  
Neuronal Excitability ◽  
Mechanical Hyperalgesia ◽  
Ovariectomized Rats ◽  
Facilitatory Effect ◽  
Transient Receptor Potential Vanilloid ◽  
Dependent Manner ◽  
Ovx Rats ◽  
17Β Estradiol

Pain symptoms in temporomandibular disorders (TMD) predominantly affect reproductive women, suggesting that estrogen regulates pain perception. However, how estrogen contributes to chronic TMD pain remains largely unclear. In the present study, we performed behavioral tests, electrophysiology, Western blot and immunofluorescence to investigate the role and underlying mechanisms of estrogen in dental experimental occlusal interference (EOI)-induced chronic masseter mechanical hyperalgesia in rats. We found that long-term 17β-estradiol (E2) replacement exacerbated EOI-induced masseter hyperalgesia in a dose-dependent manner in ovariectomized (OVX) rats. Whole-cell patch-clamp recordings demonstrated that E2 (100 nM) treatment enhanced the excitability of isolated trigeminal ganglion (TG) neurons in OVX and OVX EOI rats, and EOI increased the functional expression of transient receptor potential vanilloid-1 (TRPV1). In addition, E2 replacement upregulated the protein expression of TRPV1 in EOI-treated OVX rats. Importantly, intraganglionic administration of the TRPV1 antagonist AMG-9810 strongly attenuated the facilitatory effect of E2 on EOI-induced masseter mechanical sensitivity. These results demonstrate that E2 exacerbated EOI-induced chronic masseter mechanical hyperalgesia by increasing TG neuronal excitability and TRPV1 function. Our study helps to elucidate the E2 actions in chronic myogenic TMD pain and may provide new therapeutic targets for relieving estrogen-sensitive pain.

Sign in / Sign up

Export Citation Format

Share Document