Estrogen prevents increased hepatic aquaporin-9 expression and glycerol uptake during starvation

2012 ◽  
Vol 302 (3) ◽  
pp. G365-G374 ◽  
Author(s):  
Janne Lebeck ◽  
Patrizia Gena ◽  
Heidi O'Neill ◽  
Mariusz T. Skowronski ◽  
Sten Lund ◽  
...  
Keyword(s):  
Metabolic Stress ◽  
Glucose Production ◽  
Estrogen Receptor Α ◽  
Endogenous Glucose Production ◽  
Female Rats ◽  
Male Rats ◽  
Aquaporin 9 ◽  
17Β Estradiol ◽  
Specific Regulation ◽  
Glycerol Uptake

In starvation, glycerol is released from adipose tissue and serves as an important precursor for hepatic gluconeogenesis. By unknown sex-specific mechanisms, women suppress the endogenous glucose production better than men and respond to metabolic stress with higher plasma glycerol levels. Hepatic glycerol uptake is facilitated by aquaporin-9 (AQP9), a broad-selectivity neutral solute channel, and represents an insulin-regulated step in supplying gluconeogenesis with glycerol. In the present study, hepatic AQP9 abundance was increased 2.6-fold in starved male rats as assessed by immunoblotting and immunohistochemistry. By contrast, starvation had no significant effect on hepatic AQP9 expression in female rats. Coordinately, plasma glycerol levels remained unchanged with starvation in male rats, whereas it was increased in female rats. The different responses to starvation were paralleled by higher glycerol permeability in basolateral hepatocyte membranes from starved male rats compared with starved females. Ovariectomy led to a starvation-response pattern identical to that observed in male rats with increased hepatic AQP9 expression and unchanged plasma glycerol levels. In cultured hepatocytes, 17β-estradiol and the selective estrogen receptor α-agonist, propyl pyrazole triol, caused a decrease in AQP9 expression. Our results support that a sex-specific regulation of the hepatic glycerol channel AQP9 during starvation contributes to the higher plasma glycerol levels observed in women during fasting and possibly results in a lower cytosolic availability of glycerol. Furthermore, the sexual dimorphism in the hepatic handling of glycerol during starvation might be explained by 17β-estradiol preventing the starvation-induced increase in hepatic AQP9 abundance.

Abstract 237: Sex-specific Regulation Of Collagen I And III Expression By 17β-estradiol In Rat Cardiac Fibroblasts: Role Of Estrogen Receptors

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Elke Dworatzek ◽  
Shokoufeh Mahmoodzadeh ◽  
Sandra Kunze ◽  
Vera Regitz-Zagrosek
Keyword(s):  
Sex Differences ◽  
Western Blot ◽  
Estrogen Receptors ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Collagen I ◽  
Female Rats ◽  
17Β Estradiol ◽  
Specific Regulation

Clinical and animal studies showed in female pressure-overloaded hearts less cardiac fibrosis and collagen I and III gene expression compared to males, suggesting an inhibitory effect of 17β-Estradiol (E2) on collagens. Therefore we investigated the role of E2 and estrogen receptors (ER) on collagen I and III expression in isolated rat cardiac fibroblasts from both sexes. Cardiac fibroblasts were isolated from adult male and female Wistar rats, and treated with E2 (10-8M), vehicle, ERα and ERβ-agonist (10-7M) and/or pre-treated with ICI 182,780 (10-5M) for 24h. Cellular localization of ER in cardiac fibroblasts with/without E2 was detected by immunofluorescence staining, and expression of both ER was determined by western blot. Expression of collagen I and III was determined by qRT-PCR and western blot. E2-treatment led to a nuclear translocation of ERα and ERβ in cardiac fibroblasts, suggesting the functional activity of ER as transcription factors. Furthermore in cardiac fibroblasts from female rats E2 led to a significant down-regulation of collagen I and III gene and protein expression. In contrast there was a significant increase of collagen I and III levels in fibroblasts isolated from male rat hearts by E2. E2-effect could be inhibited by ICI 182, 780 indicating the involvement of ER. In cardiac fibroblasts from female rats, ERα-agonist treatment led to a significant down-regulation of collagen I and III mRNA level, but ERβ-agonist had no effects. In contrast, ERβ-agonist treatment of cardiac fibroblasts from males increased collagen I and III mRNA, but no changes with ERα agonist-treatment were detected. ERα protein levels displayed no sex differences at basal level. After E2-treatment ERα protein was up-regulated in male cells, but decreased in cardiac fibroblasts from females. ERβ protein was higher in female cells compared to males, but the expression was not regulated by E2 in both sexes. Sex-specific regulation of collagen I and III expression by E2 in cardiac fibroblasts might be responsible for sex-differences in cardiac fibrosis. This might be due to sexually dimorphic ER expression and regulation. Understanding how E2 and ER mediate sex-differences in cardiac remodeling may help to design sex-specific pharmacological interventions.

scholarly journals Risk-based Decision Making in Rats: Modulation by Sex and Amphetamine

2020 ◽  
Author(s):  
Dannia Islas-Preciado ◽  
Steven R. Wainwright ◽  
Julia Sniegocki ◽  
Stephane E. Lieblich ◽  
Shunya Yagi ◽  
...  
Keyword(s):  
Decision Making ◽  
Sex Differences ◽  
Gonadal Hormones ◽  
Risky Choice ◽  
Female Rats ◽  
Male Rats ◽  
Risky Decision Making ◽  
Risky Decision ◽  
17Β Estradiol ◽  
Males And Females

AbstractDecision-making is a complex process essential to daily adaptation in many species. Risk is an inherent aspect of decision-making and it is influenced by gonadal hormones. Testosterone and 17β-estradiol may modulate decision making and impact the mesocorticolimbic dopamine pathway. Here, we explored sex differences, the effect of gonadal hormones and the dopamine agonist amphetamine on risk-based decision making. Intact or gonadectomised (GDX) male and female rats underwent to a probabilistic discounting task. High and low doses of testosterone propionate (1.0 or 0.2 mg) and 17β-estradiol benzoate (0.3 μg) were administered to assess acute effects on risk-based decision making. After 3-days of washout period, intact and GDX rats received high or low (0.5 or 0.125 mg/kg) doses of amphetamine and re-tested in the probabilistic discounting task. Under baseline conditions, males made more risky choices during probability discounting compared to female rats, particularly in the lower probability blocks, but GDX did not influence risky choice. The high, but not the low dose, of testosterone modestly reduced risky decision making in GDX male rats. Conversely, 17β-estradiol had no significant effect on risky choice regardless of GDX status in either sex. Lastly, a higher dose of amphetamine increased risky decision making in both intact males and females, but had no effect in GDX rats. These findings demonstrated sex differences in risk-based decision making, with males showing a stronger bias towards larger, uncertain rewards. GDX status influenced the effects of amphetamine, suggesting different dopaminergic regulation in risk-based choices among males and females.

Salutary effects of 17β-estradiol on T-cell signaling and cytokine production after trauma-hemorrhage are mediated primarily via estrogen receptor-α

2007 ◽  
Vol 292 (6) ◽  
pp. C2103-C2111 ◽  
Author(s):  
Takao Suzuki ◽  
Tomoharu Shimizu ◽  
Huang-Ping Yu ◽  
Ya-Ching Hsieh ◽  
Mashkoor A. Choudhry ◽  
...  
Keyword(s):  
T Cells ◽  
Estrogen Receptor ◽  
T Cell ◽  
Signaling Pathways ◽  
Cytokine Production ◽  
Estrogen Receptor Α ◽  
Male Rats ◽  
17Β Estradiol ◽  
Ifn Γ ◽  
Cell Cytokine Production

Although 17β-estradiol (E2) administration following trauma-hemorrhage prevents the suppression in splenocyte cytokine production, it remains unknown whether the salutary effects of 17β-estradiol are mediated via estrogen receptor (ER)-α or ER-β. Moreover, it is unknown which signaling pathways are involved in 17β-estradiol's salutary effects. Utilizing an ER-α- or ER-β-specific agonist, we examined the role of ER-α and ER-β in E2-mediated restoration of T-cell cytokine production following trauma-hemorrhage. Moreover, since MAPK, NF-κB, and activator protein (AP)-1 are known to regulate T-cell cytokine production, we also examined the activation of MAPK, NF-κB, and AP-1. Male rats underwent trauma-hemorrhage (mean arterial pressure 40 mmHg for 90 min) and fluid resuscitation. ER-α agonist propyl pyrazole triol (PPT; 5 μg/kg), ER-β agonist diarylpropionitrile (DPN; 5 μg/kg), 17β-estradiol (50 μg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. Twenty-four hours thereafter, splenic T cells were isolated, and their IL-2 and IFN-γ production and MAPK, NF-κB, and AP-1 activation were measured. T-cell IL-2 and IFN-γ production was decreased following trauma-hemorrhage, and this was accompanied with a decrease in T-cell MAPK, NF-κB, and AP-1 activation. PPT or 17β-estradiol administration following trauma-hemorrhage normalized those parameters, while DPN administration had no effect. Since PPT, but not DPN, administration following trauma-hemorrhage was as effective as 17β-estradiol in preventing the T-cell suppression, it appears that ER-α plays a predominant role in mediating the salutary effects of 17β-estradiol on T cells following trauma-hemorrhage, and that such effects are likely mediated via normalization of MAPK, NF-κB, and AP-1 signaling pathways.

Effects of lactate on glucose metabolism in healthy subjects and in severely injured hyperglycemic patients

1995 ◽  
Vol 268 (4) ◽  
pp. E630-E635 ◽  
Author(s):  
L. Tappy ◽  
M. C. Cayeux ◽  
P. Schneiter ◽  
C. Schindler ◽  
E. Temler ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Multiple Trauma ◽  
Hepatic Glucose Production ◽  
Metabolic Stress ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Carbohydrate Oxidation ◽  
Exogenous Glucose ◽  
Hepatic Glucose ◽  
Endogenous Glucose

Hepatic glucose production is autoregulated during infusion of gluconeogenic precursors. In hyperglycemic patients with multiple trauma, hepatic glucose production and gluconeogenesis are increased, suggesting that autoregulation of hepatic glucose production may be defective. To better understand the mechanisms of autoregulation and its possible alterations in metabolic stress, lactate was coinfused with glucose in healthy volunteers and in hyperglycemic patients with multiple trauma or critical illness. In healthy volunteers, infusion of glucose alone nearly abolished endogenous glucose production. Lactate increased gluconeogenesis (as indicated by a decrease in net carbohydrate oxidation with no change in total [13C]carbohydrate oxidation) but did not increase endogenous glucose production. In patients with metabolic stress, endogenous glucose production was not suppressed by exogenous glucose, but lactate did not further increase hepatic glucose production. It is concluded that 1) in healthy humans, autoregulation of hepatic glucose production during infusion of lactate is still present when glycogenolysis is suppressed by exogenous glucose and 2) autoregulation of hepatic glucose production is not abolished in hyperglycemic patients with metabolic stress.

scholarly journals Sex differences in depression-like behavior and neuroinflammation in rats post-MI: role of estrogens

2018 ◽  
Vol 315 (5) ◽  
pp. H1159-H1173 ◽  
Author(s):  
Fatimah Najjar ◽  
Monir Ahmad ◽  
Diane Lagace ◽  
Frans H. H. Leenen
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Sex Differences ◽  
Prefrontal Cortex ◽  
Young Adult ◽  
Female Rats ◽  
Male Rats ◽  
Mild Depression ◽  
Cytokine Levels ◽  
17Β Estradiol

Patients with heart failure (HF) have a high prevalence of depression associated with a worse prognosis, particularly in older women. The present study evaluated whether sex and estrogens affect depression-like behavior and associated neuroinflammation induced by myocardial infarction (MI) in rats. MI was induced by occlusion of the left anterior descending artery in young adult male and female Wistar rats or in ovariectomized (OVX) female rats without and with estrogen [17β-estradiol (E2)] replacement. MI groups showed a comparable degree of cardiac dysfunction. Eight weeks post-MI, male rats with HF exhibited depression-like behaviors, including anhedonia and higher immobility in the sucrose preference and forced swim tests, which were not observed in female rats with HF. In the cued fear conditioning test, male but not female rats with HF froze more than sham rats. After OVX, female sham rats developed mild depression-like behaviors that were pronounced in OVX female rats post-MI and were largely prevented by E2 replacement. Cytokine levels in the plasma and paraventricular nucleus increased in both sexes with HF, but only male rats with HF showed an increase in cytokine levels in the prefrontal cortex. OVX alone did not affect cytokine levels, but OVX-MI caused significant increases in the prefrontal cortex, which were shifted to an anti-inflammatory pattern by E2 replacement. These results suggest that estrogens prevent depression-like behavior induced by HF post-MI in young adult female rats by inhibiting proinflammatory cytokine production and actions in the prefrontal cortex. NEW & NOTEWORTHY In contrast to male rats, female rats with heart failure after myocardial infarction do not develop depression-like behavior or increases in prefrontal cortex cytokines. However, after ovariectomy, female rats exhibit similar changes, which are prevented by 17β-estradiol replacement. Neuroinflammation in the prefrontal cortex in male subjects may contribute to depression-like behavior, whereas its estrogen-dependent absence in female subjects may protect against depression. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/sex-differences-in-depression-like-behavior-post-myocardial-infarction/ .

Ligand-specific regulation of proteasome-mediated proteolysis of estrogen receptor-α

2002 ◽  
Vol 282 (4) ◽  
pp. E891-E898 ◽  
Author(s):  
Mara T. Preisler-Mashek ◽  
Natalia Solodin ◽  
Bethany L. Stark ◽  
Michael K. Tyriver ◽  
Elaine T. Alarid
Keyword(s):  
Estrogen Receptor ◽  
Ligand Binding ◽  
Binding Affinity ◽  
Binding Pocket ◽  
Estrogen Receptor Α ◽  
Activation Of Transcription ◽  
Receptor Concentration ◽  
17Β Estradiol ◽  
Specific Regulation ◽  
Multiple Receptor

Proteasome-mediated proteolysis modulates the cellular concentration of estrogen receptor-α (ERα) and is induced by treatment of cells with 17β-estradiol. Herein, we show that multiple receptor agonists, including 17α-estradiol and estriol as well as the antagonist ICI-182780, stimulate proteasome-dependent proteolysis of ERα in a process that requires ligand binding to the receptor. Proteolysis of receptor depends on ligand concentration, and there exists a direct correlation between ligand-binding affinity and the half-maximal dose of ligand required to stimulate receptor degradation. Furthermore, introduction of a point mutation into the receptor ligand-binding pocket yields a stable receptor resistant to proteolysis. Interestingly, although all ligands stimulate receptor degradation, the extent to which overall ER levels are affected varies with each ligand and is not related to ligand-binding affinity or activation of transcription. These results demonstrate ligand-specific regulation of ERα proteolysis, and they introduce the concept that cellular receptor concentration is governed not only at the level of induction of proteolysis but also by the efficiency with which the receptor is degraded.

Estrogen therapy for experimental intracerebral hemorrhage in rats

2005 ◽  
Vol 103 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Takehiro Nakamura ◽  
Ya Hua ◽  
Richard F. Keep ◽  
Jung-Weon Park ◽  
Guohua Xi ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Estrogen Therapy ◽  
Female Rats ◽  
Male Rats ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Autologous Whole Blood ◽  
17Β Estradiol

Object The aims of this study were to determine the following: whether there are sex differences in intracerebral hemorrhage (ICH) induced brain injury in rats, whether delayed administration of 17β-estradiol can reduce ICH-induced brain damage, and whether these effects are estrogen receptor (ER)-dependent. Methods Male and female Sprague—Dawley rats received an infusion of 100 µl autologous whole blood into the right basal ganglia. Twenty-four hours later the rats were killed. The effects of 17β-estradiol on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Both ER-α and hemeoxygenase (HO)-1 were investigated through Western blot and immunohistochemical analysis. Brain edema was significantly less severe in female compared with that in male rats. The ER antagonist ICI 182,780 exacerbated ICH-induced brain edema in female but not in male rats, indicating that ER-α activation during ICH is protective in female rats. Administration of exogenous 17β-estradiol in male, but not in female, rats significantly attenuated brain edema, neurological deficits, and ICH-induced changes in HO-1 when given 2 hours after hemorrhage. The effects of exogenous 17β-estradiol occurred through an ER-independent mechanism. Conclusions Results in this study indicate that 17β-estradiol could be a potential therapeutic agent for ICH.

Change from beta- to alpha-adrenergic glycogenolysis induced by corticosteroids in female rat liver

1997 ◽  
Vol 273 (1) ◽  
pp. R153-R160
Author(s):  
M. Moriyama ◽  
Y. Nakanishi ◽  
S. Tsuyama ◽  
Y. Kannan ◽  
M. Ohta ◽  
...  
Keyword(s):  
Glucose Production ◽  
Plasma Corticosterone ◽  
Mature Female ◽  
Female Rats ◽  
Male Rats ◽  
Female Rat ◽  
Circadian Variations ◽  
Male And Female ◽  
Male And Female Rats ◽  
The Difference

The conversion of beta- to alpha-adrenergic glycogenolysis by corticosteroids was studied in perfused livers of mature female rats. Isoproterenol stimulated glucose production more effectively in female rats than in male rats, but the difference in its stimulatory effect disappeared in adrenalectomized (ADX) rats, whereas it remained in adrenodemedulated rats. When ADX female rats were treated with dexamethasone sulfate, alpha-responses increased and beta-responses decreased, depending on the concentration of dexamethasone sulfate. The treatment of female rats with 1.5 mg/kg dexamethasone sulfate changed the levels of the alpha- and beta-responses to those observed in male rats, and the changes were associated with changes in the number of receptors. Although periodicity of changes in plasma corticosterone levels was observed in both male and female rats, the extent of circadian variations was significantly lower in female rats during the estrous cycle than in male rats. The variations in plasma corticosterone levels and in both alpha- and beta-responses after ovariectomy approached those in male rats. The results suggest that the level of plasma corticosterone might play an important role in the regulation of the relative levels of alpha- and beta-adrenergic responses in female rats.

Effects of galanin-like peptide on luteinizing hormone secretion in the rat: sexually dimorphic responses and enhanced sensitivity at male puberty

2006 ◽  
Vol 291 (6) ◽  
pp. E1281-E1289 ◽  
Author(s):  
J. M. Castellano ◽  
V. M. Navarro ◽  
R. Fernández-Fernández ◽  
J. Roa ◽  
E. Vigo ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Hormone Secretion ◽  
Metabolic Stress ◽  
Female Rats ◽  
Metabolic Status ◽  
Male Rats ◽  
Intracerebral Injection ◽  
Luteinizing Hormone Secretion ◽  
Male Puberty ◽  
Lh Secretion

Reproductive function is exquisitely sensitive to adequacy of nutrition and fuel reserves, through mechanisms that are yet to be completely elucidated. Galanin-like peptide (GALP) has recently emerged as another neuropeptide link that couples reproduction and metabolism. However, although the effects of GALP on luteinizing hormone (LH) secretion have been studied, no systematic investigation on how these responses might differ along sexual maturation and between sexes has been reported. Moreover, the influence of metabolic status and potential interplay with other relevant neurotransmitters controlling LH secretion remain ill defined. These facets of GALP physiology were addressed herein. Intracerebral injection of GALP to male rats induced a dose-dependent increase in serum LH levels, the magnitude of which was significantly greater in pubertal than in adult males. In contrast, negligible LH responses to GALP were detected in pubertal or adult female rats at diestrus. Neonatal androgen treatment to females failed to “masculinize” the pattern of LH response to GALP. In addition, metabolic stress by short-term fasting did not prevent but rather amplified LH responses to GALP in pubertal males, whereas these responses were abrogated by pharmacological inhibition of nitric oxide synthesis. We conclude that the ability of GALP to evoke LH secretion is sexually differentiated, with maximal responses at male puberty, a phenomenon which was not reverted by manipulation of sex steroid milieu during the critical neonatal period and was sensitive to metabolic stress. This state of LH hyperresponsiveness may prove relevant for the mechanisms relaying metabolic status to the reproductive axis in male puberty.

scholarly journals Opposite Effects of Androgens and Estrogens on Adipogenesis in Rat Preadipocytes: Evidence for Sex and Site-Related Specificities and Possible Involvement of Insulin-Like Growth Factor 1 Receptor and Peroxisome Proliferator-Activated Receptorγ 21

Endocrinology ◽  
2000 ◽  
Vol 141 (2) ◽  
pp. 649-656 ◽  
Author(s):  
M. N. Dieudonne ◽  
R. Pecquery ◽  
M. C. Leneveu ◽  
Y. Giudicelli
Keyword(s):  
Growth Factor ◽  
Dehydrogenase Activity ◽  
Sex Steroids ◽  
Female Rats ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
17Β Estradiol ◽  
Glycerol 3 Phosphate Dehydrogenase

Abstract To investigate the role of sex steroid hormones in adipose tissue development and distribution, we have studied the effect of various sex steroids (testosterone, dihydrotestosterone (DHT), and 17β-estradiol) in vitro, on the proliferation and differentiation processes in rat preadipocytes from deep (epididymal and parametrial) and superficial (femoral sc) fat deposits. All added steroids failed to affect the growth rate of preadipocytes from male rats when determined from day 1 to day 4 after plating, whether FCS was present or not in the culture medium. In contrast, in preadipocytes from female rats, we observed a positive effect (×2) of 17β-estradiol (0.01μ m) on the proliferative capacities of sc but not parametrial preadipocytes. When preadipocytes were exposed to testosterone or DHT (0.1 μm) during the differentiation process, the glycerol 3-phosphate dehydrogenase activity was significantly decreased in epididymal preadipocytes only. When preadipocytes from male rats were exposed to 17β-estradiol (0.01μ m), the differentiation capacities of preadipocytes were not modified. However, in parametrial preadipocytes from ovariectomized female rats, 17β-estradiol significantly increased (×1.34) the glycerol 3-phosphate dehydrogenase activity. In differentiated preadipocytes that had been exposed to sex steroids, expression of peroxisome proliferator-activated receptor γ2 was up-regulated by 17β-estradiol but not by androgens. As described in other cell types, sex steroids modulate insulin growth factor 1 receptor (IGF1R) expression in preadipocytes. Indeed, IGF1R levels were either enhanced by 17 β-estradiol (0.01 μm) in sc preadipocytes from female ovariectomized rats or decreased by DHT (0.01 μm) in epididymal preadipocytes. These effects were reversed by simultaneous exposure to androgen or estrogen receptor antagonists. In conclusion, this study demonstrates that, in rat preadipocytes kept in primary culture and chronically exposed to sex hormones, androgens elicit an antiadipogenic effect, whereas estrogens behave as proadipogenic hormones. Moreover, our results suggest that these opposite effects could be related to changes in IGF1R (androgens and estrogens) and peroxisome proliferator-activated receptor γ2 expression (estrogens).

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