scholarly journals Effects of the loss of estrogen on the heart’s hypertrophic response to chronic left ventricle volume overload in rats

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7924 ◽  
Author(s):  
Elisabeth Walsh-Wilkinson ◽  
Catherine Beaumont ◽  
Marie-Claude Drolet ◽  
Ève-Marie Roy ◽  
Charlie Le Houillier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Left Ventricle ◽  
Natriuretic Peptide ◽  
Systolic Function ◽  
Volume Overload ◽  
The Other ◽  
Female Rats ◽  
Hypertrophic Response ◽  
Other Hand ◽  
Ovx Rats

Aortic valve regurgitation (AR) can result in heart failure from chronic overloading of the left ventricle (LV). Little is known of the role of estrogens in the LV responses to this condition. The aim of the study was to compare LV remodeling in female rats with severe AR in absence of estrogens by ovariectomy (Ovx). In a first study, we investigated over 6 months the development of hypertrophy in four groups of female Wistar rats: AR or sham-operated (sham) and Ovx or not. Ovx reduced normal heart growth. As expected, volume overload (VO) from AR resulted in significant LV dilation (42% and 32% increase LV end-diastolic diameter in intact and Ovx groups vs. their respective sham group; p < 0.0001). LV weight was also significantly and similarly increased in both AR groups (non-Ovx and Ovx). Increase in stroke volume or cardiac output and loss of systolic function were similar between AR intact and AR Ovx groups compared to sham. We then investigated what were the effects of 17beta-estradiol (E2; 0.03 mg/kg/day) treatment on the parameters studied in Ovx rats. Ovx reduced uterus weight by 85% and E2 treatment restored up to 65% of the normal weight. E2 also helped normalize heart size to normal values. On the other hand, it did not influence the extent of the hypertrophic response to AR. In fact, E2 treatment further reduced LV hypertrophy in AR Ovx rats (41% over Sham Ovx + E2). Systolic and diastolic functions parameters in AR Ovx + E2 were similar to intact AR animals. Ovx in sham rats had a significant effect on the LV gene expression of several hypertrophy markers. Atrial natriuretic peptide (Nppa) gene expression was reduced by Ovx in sham-operated females whereas brain natriuretic peptide (Nppb) expression was increased. Alpha (Myh6) and beta (Myh7) myosin heavy chain genes were also significantly modulated by Ovx in sham females. In AR rats, LV expression of both Nppa and Nppb genes were increased as expected. Ovx further increased it of AR rats for Nppa and did the opposite for Nppb. Interestingly, AR in Ovx rats had only minimal effects on Myh6 and Myh7 genes whereas they were modulated as expected for intact AR animals. In summary, loss of estrogens by Ovx in AR rats was not accompanied by a worsening of hypertrophy or cardiac function. Normal cardiac growth was reduced by Ovx in sham females but not the hypertrophic response to AR. On the other hand, Ovx had important effects on LV gene expression both in sham and AR female rats.

scholarly journals USF1 and USF2 Mediate Inhibition of Human Trophoblast Differentiation and CYP19 Gene Expression by Mash-2 and Hypoxia

2003 ◽  
Vol 23 (17) ◽  
pp. 6117-6128 ◽  
Author(s):  
Bing Jiang ◽  
Carole R. Mendelson
Keyword(s):  
Gene Expression ◽  
Dna Binding ◽  
Promoter Activity ◽  
Leucine Zipper ◽  
Binding Activity ◽  
The Other ◽  
Mrna Levels ◽  
Human Trophoblast ◽  
Other Hand ◽  
E Boxes

ABSTRACT In the human placental syncytiotrophoblast, C19 steroids are converted to estrogens by aromatase P450, product of the CYP19 gene. When human cytotrophoblasts, which lack the capacity to express aromatase, are cultured in 20% O2, they spontaneously fuse to form a multinuclear syncytiotrophoblast and CYP19 expression is markedly induced. On the other hand, when cytotrophoblasts are cultured in 2% O2, syncytiotrophoblast differentiation and induction of CYP19 expression are prevented. We previously observed that expression of the transcription factor Mash-2 (mammalian achaete/scute homologue 2), which is elevated in human cytotrophoblasts and maintained at elevated levels by hypoxia, declines with syncytiotrophoblast differentiation. Overexpression of Mash-2 prevents syncytiotrophoblast differentiation and induction of CYP19 expression. In the present study, we observed that unexpectedly immunoreactive Mash-2 protein was localized predominately to the cytoplasm of human cytotrophoblasts. Elevated cytoplasmic levels of Mash-2 were maintained when trophoblasts were cultured in 2% O2 and declined to undetectable levels upon culture in 20% O2. Previously, we found that Mash-2 inhibited CYP19 promoter activity through sequences within a 350-bp region upstream and within placenta-specific exon I.1 containing three E boxes (E1 at −325 bp, 5′-CACTTG-3′; E2 at −58 bp, 5′-CACATG-3′; and E3 at +26 bp, 5′-CACGTG-3′). In this study, we found that trophoblast nuclear protein binding to these E boxes declined with syncytiotrophoblast differentiation in 20% O2 and was induced by hypoxia; however, Mash-2 did not appear to bind to any of these E boxes. On the other hand, the basic helix-loop-helix leucine zipper transcription factors upstream stimulatory factors 1 and 2 (USF1 and USF2) did bind to E2 and E3 but not E1. Nuclear levels of USF1 and USF2 and DNA-binding activity declined with syncytiotrophoblast differentiation and were maintained at elevated levels by hypoxia and overexpression of Mash-2, whereas USF1 mRNA levels were unaffected. Finally, USF1 overexpression in cultured human trophoblasts markedly inhibited endogenous CYP19 expression, differentiation of cultured human trophoblast cells, and CYP19 promoter activity. These findings suggest that increased protein levels and DNA binding of USF1 and USF2 mediate the inhibitory effects of hypoxia and of Mash-2 on CYP19 gene expression in human placenta.

scholarly journals Female rats with severe left ventricle volume overload exhibit more cardiac hypertrophy but fewer myocardial transcriptional changes than males

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Catherine Beaumont ◽  
Élisabeth Walsh-Wilkinson ◽  
Marie-Claude Drolet ◽  
Élise Roussel ◽  
Marie Arsenault ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Cardiac Hypertrophy ◽  
Volume Overload ◽  
Female Rats ◽  
Left Ventricle Volume ◽  
Transcriptional Changes ◽  
Ventricle Volume

scholarly journals Predominant androgenic component in the stimulatory effect of dehydroepiandrosterone on bone mineral density in the rat

1998 ◽  
Vol 157 (3) ◽  
pp. 433-442 ◽  
Author(s):  
C Martel ◽  
A Sourla ◽  
G Pelletier ◽  
C Labrie ◽  
M Fournier ◽  
...  
Keyword(s):  
Trabecular Bone ◽  
Bone Mineral ◽  
Bone Volume ◽  
The Other ◽  
Female Rats ◽  
Trabecular Bone Volume ◽  
A Value ◽  
Other Hand ◽  
Dhea Treatment ◽  
Trabecular Number

In order to assess the relative roles of the androgenic and/or estrogenic components in the stimulatory effect of dehydroepiandrosterone (DHEA) on bone mineral content (BMC) and density (BMD), ovariectomized (OVX) female rats received DHEA administered alone or in combination with the antiandrogen flutamide (FLU) or the antiestrogen EM-800 for 12 months. We also evaluated, for comparison, the effect of estradiol (E2) and dihydrotestosterone (DHT) constantly released by Silastic implants as well as medroxyprogesterone acetate (MPA) released from poly(lactide-co-glycolide) microspheres. Femoral BMD was decreased by 11% 1 year after OVX, but treatment of OVX animals with DHEA increased BMD to a value 8% above that of intact animals. The administration of FLU reversed by 76% the stimulatory effect of DHEA on femoral BMD and completely prevented the stimulatory effect of DHEA on total body and lumbar spine BMD. Similar results were obtained for BMC. On the other hand, treatment with the antiestrogen EM-800 did not reduce the action of DHEA on BMD or BMC. At the doses used, MPA, E2 and DHT increased femoral BMD, but to a lesser degree than observed with DHEA. Bone histomorphometry measurements were also performed. While DHEA treatment partially reversed the marked inhibitory effect of OVX on the tibial trabecular bone volume, the administration of FLU inhibited by 51% (P < 0.01) the stimulatory effect of DHEA on this parameter. The addition of EM-800 to DHEA, on the other hand, increased trabecular bone volume to a value similar to that of intact controls. DHEA administration markedly increased trabecular number while causing a marked decrease in the intertrabecular area. The above stimulatory effect of DHEA on trabecular number was reversed by 54% (P < 0.01) by the administration of FLU, which also reversed by 29% the decrease in intertrabecular area caused by DHEA administration. On the other hand, the addition of EM-800, while further decreasing the intertrabecular space achieved by DHEA treatment, also led to a further increase in trabecular number to a value not significantly different from that of intact control animals, suggesting an additional effect of EM-800 over that achieved by DHEA. Treatment with DHEA caused a 4-fold stimulation of serum alkaline phosphatase, a marker of bone formation, while the urinary excretion of hydroxyproline, a marker of bone resorption, was decreased by DHEA treatment. Treatment with DHEA and DHEA + EM-800 decreased serum cholesterol levels by 22 and 65% respectively, while the other treatments had no significant effect on this parameter. The present data indicate that the potent stimulatory effect of DHEA on bone in the rat is mainly due to the local formation of androgens in bone cells and their intracrine action in osteoblasts.

scholarly journals C-Type Natriuretic Peptide Ameliorates Lipopolysaccharide-Induced Cardiac Dysfunction in Rats with Pulmonary Arterial Hypertension

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Xiaowei Gao ◽  
Maoen Zhu ◽  
Yanan Cao ◽  
Yue Yang ◽  
Zhi Ye ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Left Ventricle ◽  
Cardiac Function ◽  
Arterial Hypertension ◽  
Natriuretic Peptide ◽  
Cardiac Dysfunction ◽  
Systolic Function ◽  
Cgmp Level ◽  
Pulmonary Arterial ◽  
Left Ventricle Systolic Function

Lipopolysaccharide induces rapid deterioration of cardiac function in rats with pulmonary arterial hypertension. It was desired to investigate if this cardiac dysfunction could be treated by C-type natriuretic peptide. Rat pulmonary arterial hypertension was induced by intraperitoneal injection of monocrotaline. Hemodynamics and cardiac function were measured by pressure-volume (P-V) catheter before and after the rats were treated with lipopolysaccharide and C-type natriuretic peptide. Cyclic guanosine 3′,5′-monophosphate (cGMP) level was determined by enzyme-linked immunosorbent assay analysis. After the rats were injected with low-dose lipopolysaccharide, they experienced left ventricle systolic function deterioration. Administration of C-type natriuretic peptide improved hemodynamics and left ventricle systolic function. cGMP level was elevated after C-type natriuretic peptide treatment. C-type natriuretic peptide could ameliorate lipopolysaccharide-induced cardiac dysfunction and restore hemodynamic deterioration in rats with pulmonary arterial hypertension.

P1247INTERDIALYTIC WEIGHT GAIN IN HEMODIALYSIS: EPIDEMIOLOGY AND OUTCOMES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Issa Al Salmi ◽  
Yacoub Al Maimani ◽  
Fady Magdy ◽  
SUAD Hannawi
Keyword(s):  
Weight Gain ◽  
Hospital Admission ◽  
Hospital Admissions ◽  
Laboratory Data ◽  
Volume Overload ◽  
The Other ◽  
Nutrition Status ◽  
Interdialytic Weight Gain ◽  
Other Hand ◽  
The Impact

Abstract Background and Aims Interdialytic weight gain (IDWG) has been linked to various complications in hemodialysis (HD) patients, especially cardiovascular (CV) complications. We aimed to evaluate the effect of IDWG in HD patients on the rate of hospital admissions over a 12-month period, and the impact of high IDWG on the frequency of IDH. Method The study included 120 patients; who had been receiving HD for at least 3 months. The presence of various comorbidities has been recorded including. Laboratory data included; serum creatinine, serum albumin, and hemoglobin level. The estimated IDWG was calculated based on the average between pre- and post- dialysis weights that were recorded on 3 consecutive dialysis sessions. Results Among those who had IDWG ≥ 4%, 81% of these patients had at least one hospital admission due to volume overload or the need for extra HD session(s). On the other hand, only 19% of those having IDWG &lt; 4% had been admitted or got extra HD sessions (p&lt;0.001). Of those who were admitted (over 12 months) due to volume overload; 74.1 % had IDWG ≥ 4%, while 25.9% had IDWG &lt; 4% (p&lt; 0.001). Regarding IDH, 87% of patients having IDWG ≥ 4% had at least one episode of IDH/week. On the other hand, only 22.5% of those with IDWG &lt; 4% had one episode of IDH/week (p&lt;0.001). When analyzing those who had at least one IDH episode/week; 72.9% of them had IDWG ≥ 4%, while only 27.1% had IDWG &lt; 4% (p&lt;0.001). Conclusion In HD patients, the frequency of hospital admission due to volume overload and the need for extra HD sessions is strongly related to the amount of IDWG (&gt; 4% in our patients), the same stands for the frequency of IDH. Thus, a control of IDWG in HD patient is of great importance, keeping in mind the importance the nutrition status of HD patients that may also impact IDWG.

scholarly journals Modulation of responses to stress by estradiol benzoate and selective estrogen receptor agonists

2010 ◽  
Vol 205 (3) ◽  
pp. 253-262 ◽  
Author(s):  
Lidia I Serova ◽  
Heather A Harris ◽  
Shreekrishna Maharjan ◽  
Esther L Sabban
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Hpa Axis ◽  
Immobilization Stress ◽  
Estradiol Benzoate ◽  
Female Rats ◽  
Reduced Body ◽  
Ovx Rats ◽  
Selective Agonists

Previously, pretreatment with estradiol benzoate (EB) was found to modulate the response of hypothalamic–pituitary–adrenal (HPA) axis and gene expression in several catecholaminergic neuronal locations in ovariectomized (OVX) rats exposed to single immobilization stress (IMO). Here, we investigated the role of estrogen receptor (ER) subtypes, using selective agonists for ERα (propyl pyrazole triol, PPT) or ERβ (WAY-200070) in two major central noradrenergic systems and the HPA axis after exposure to single and repeated IMO. OVX female rats received 21 daily injections of either EB (25 μg/kg), PPT (10 mg/kg), WAY-200070 (10 mg/kg), or vehicle. Injections of EB and PPT, but not WAY-200070, elicited reduced body weight and increased uterine weight, showing their selectivity. Both EB and PPT increased corticosterone levels about two- to threefold, but prevented any further rise with either single or repeated IMO, indicating an ERα (ESR1)-, but not ERβ (ESR2)-, mediated mechanism. In the locus coeruleus (LC), the rise in dopamine-β-hydroxylase (Dbh) mRNA with both stress paradigms was abrogated in EB- or PPT-injected animals. However, WAY-200070 blocked the response of DBH mRNA to single IMO but not to repeated IMO. In the nucleus of the solitary tract (NTS), the rise in tyrosine hydroxylase and DBH mRNAs with both IMOs was absent, or greatly attenuated, in EB- or PPT-treated rats. In most cases, WAY-200070 inhibited the response to single IMO but not to repeated IMO. The results demonstrate that pretreatment with estradiol, or ER-selective agonists, modulates the stress-triggered induction of gene expression of norepinephrine biosynthetic enzymes in LC and NTS, with ER selectivity depending on duration of the stress.

THE UPTAKE OF 17β-OESTRADIOL IN BREAST TISSUE OF FEMALE RATS

1968 ◽  
Vol 58 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Sten Sander
Keyword(s):  
Skeletal Muscle ◽  
Direct Effect ◽  
Breast Tissue ◽  
The Other ◽  
Female Rats ◽  
Competitive Effect ◽  
Simultaneous Injection ◽  
Other Hand ◽  
Uptake Pattern ◽  
Wet Weight

ABSTRACT The uptake of radioactivity in breast tissue after the injection of tritiated oestradiol in rats has been studied. The breast tissue accumulates more radioactivity per unit wet weight than skeletal muscle and fat, for at least 4 hours. The uptake of radioactivity does not, however, reach the high levels observed in the uterus. On the other hand, the uptake pattern found in the breast tissue corresponds to previous findings in other oestrogen responsive organs. The uptake of radioactivity by breast tissue in castrated rats is higher than in control animals with their ovaries intact. It is also found that simultaneous injection of non-radioactive oestradiol reduces the uptake of radioactivity. These findings may be explained as a competitive effect between non-labelled and labelled oestradiol. The accumulation of oestradiol observed may be consistent with the idea of a direct effect on breast tissue.

Persisting mild hypothermia suppresses hypoxia-inducible factor-1α protein synthesis and hypoxia-inducible factor-1-mediated gene expression

2010 ◽  
Vol 298 (3) ◽  
pp. R661-R671 ◽  
Author(s):  
Tomoharu Tanaka ◽  
Takuhiko Wakamatsu ◽  
Hiroki Daijo ◽  
Seiko Oda ◽  
Shinichi Kai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Low Temperature ◽  
Hypoxia Inducible Factor ◽  
The Body ◽  
The Other ◽  
Adaptation To Hypoxia ◽  
Hypoxia Inducible Factor 1 ◽  
Other Hand

The transcription factor hypoxia-inducible factor-1 (HIF-1) plays an essential role in regulating gene expression in response to hypoxia-ischemia. Ischemia causes the tissue not only to be hypoxic but also to be hypothermic because of the hypoperfusion under certain circumstances. On the other hand, the induced hypothermia is one of the most common therapeutic modalities to extend tolerance to hypoxia. Although hypoxia elicits a variety of cellular and systemic responses at different organizational levels in the body, little is known about how hypoxia-induced responses are affected by low temperature. We examined the influence of mild hypothermic conditions (28–32°C) on HIF-1 in both in vitro and in vivo settings. In vitro experiments adopting cultured cells elucidated that hypoxia-induced HIF-1 activation was resistant to 4-h exposure to the low temperature. In contrast, exposure to the low temperature as long as 24 h suppressed HIF-1 activation and the subsequent upregulation of HIF-1 target genes such as VEGF or GLUT-1. HIF-1α protein stability in the cell was not affected by hypothermic treatment. Furthermore, intracellular ATP content was reduced under 1% O2 conditions but was not largely affected by hypothermic treatment. The evidence indicates that reduction of oxygen consumption is not largely involved in suppression of HIF-1. In addition, we demonstrated that HIF-1 DNA-binding activity and HIF-1-dependent gene expressions induced under 10% O2 atmosphere in mouse brain were not influenced by treatment under 3-h hypothermic temperature but were inhibited under 5-h treatment. On the other hand, we indicated that warming ischemic legs of mice for 24 h preserved HIF-1 activity. In this report we describe for the first time that persisting low temperature significantly reduced HIF-1α neosynthesis under hypoxic conditions, leading to a decrease in gene expression for adaptation to hypoxia in both in vitro and in vivo settings.

Short Term Effects on Bone Quality Associated with Consumption of Soy Protein Isolate and Other Dietary Protein Sources in Rapidly Growing Female Rats

2008 ◽  
Vol 233 (11) ◽  
pp. 1348-1358 ◽  
Author(s):  
Jin-Ran Chen ◽  
Rohit Singhal ◽  
Oxana P. Lazarenko ◽  
Xiaoli Liu ◽  
William R. Hogue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Quality ◽  
Soy Protein ◽  
Dietary Protein ◽  
Soy Protein Isolate ◽  
Protein Isolate ◽  
Female Rats ◽  
Protein Sources ◽  
Positive Effects ◽  
Ovx Rats

Beneficial effects of soy protein consumption on bone quality have been reported. The effects of other dietary protein sources such as whey protein hydrolysate (WPH) and rice protein isolate (RPI) on bone growth have been less well examined. The current study compared effects of feeding soy protein isolate (SPI), WPH and RPI for 14 d on tibial bone mineral density (BMD) and bone mineral content (BMC) in intact and ovariectomized (OVX) rapidly growing female rats relative to animals fed casein (CAS). The effects of estrogenic status on responses to SPI were also explored. Tibial peripheral quantitative computerized tomography (pQCT) showed all three protein sources had positive effects on either BMD or BMC relative to CAS ( P < 0.05), but SPI had greater effects in both intact and OVX female rats. SPI and E2 had positive effects on BMD and BMC in OVX rats ( P < 0.05). However, trabecular BMD was lower in a SPI + E2 group compared to a CAS + E2 group. In OVX rats, SPI increased serum bone formation markers, and serum from SPI-fed rats stimulated osteoblastogenesis in ex vivo. SPI also suppressed the bone resorption marker RatLaps ( P < 0.05). Both SPI and E2 increased alkaline phosphatase gene expression in bone, but only SPI decreased receptor activator of nuclear factor-κB ligand (RANKL) and estrogen receptor gene expression ( P < 0.05). These data suggest beneficial bone effects of a soy diet in rapidly growing animals and the potential for early soy consumption to increase peak bone mass.

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