scholarly journals Estradiol Enhances Cholecystokinin-Dependent Lipid-Induced Satiation and Activates Estrogen Receptor-α-Expressing Cells in the Nucleus Tractus Solitarius of Ovariectomized Rats

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5656-5666 ◽  
Author(s):  
Lori Asarian ◽  
Nori Geary
Keyword(s):  
Estrogen Receptor ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Significant Proportion ◽  
Estradiol Benzoate ◽  
Estrogen Receptor Α ◽  
Male Rats ◽  
Ovariectomized Rats ◽  
Vehicle Injection ◽  
Arcuate Nuclei

Part of the mechanism through which estradiol, acting via estrogen receptor (ERα) signaling, inhibits feeding in rats and mice is increasing the satiating potency of cholecystokinin (CCK) acting on peripheral CCK-1 receptors. Ingested lipid is a principal secretagogue of intestinal CCK, and intraduodenal lipid infusions elicit CCK-mediated satiation in animals and humans. Here we tested whether estradiol affects the satiating potency of intraduodenal lipid infusions in ovariectomized rats and, using c-Fos immunocytochemistry, searched for potential brain sites of ERα involved. Food-deprived ovariectomized rats with open gastric cannulas sham fed 0.8 m sucrose 2 d after estradiol (estradiol benzoate, 10 μg, sc) or vehicle injection. Estradiol markedly increased the satiating potency of intraduodenal infusions of Intralipid but not the satiating potency of L-phenylalanine (10 min infusions, 0.44 ml/min, 0.13 kcal/ml), which in male rats satiates via a CCK-independent mechanism. Estradiol had no significant effect in rats pretreated with the CCK-1 receptor antagonist Devazepide (1 mg/kg, ip). The effect of estradiol on intraduodenal Intralipid-induced satiation was mirrored by selective increases in the number of cells expressing c-Fos immunoreactivity in a circumscribed region of the nucleus tractus solitarius (NTS), just caudal to the area postrema (cNTS) but not elsewhere in the NTS or the hypothalamic paraventricular or arcuate nuclei. In addition, a significant proportion of cNTS c-Fos-positive cells also expressed ERα. These data provide behavioral and cellular evidence that estradiol-ERα signaling in cNTS neurons increases the satiating potency of endogenous CCK released in response to ingested lipid.

scholarly journals Hindbrain Administration of Estradiol Inhibits Feeding and Activates Estrogen Receptor-α-Expressing Cells in the Nucleus Tractus Solitarius of Ovariectomized Rats

Endocrinology ◽  
2007 ◽  
Vol 149 (4) ◽  
pp. 1609-1617 ◽  
Author(s):  
Sumpun Thammacharoen ◽  
Thomas A. Lutz ◽  
Nori Geary ◽  
Lori Asarian
Keyword(s):  
Estrogen Receptor ◽  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Estradiol Benzoate ◽  
Estrogen Receptor Α ◽  
Ovariectomized Rats ◽  
Afferent Projections ◽  
Inhibit Food Intake ◽  
17Β Estradiol ◽  
Direct Administration

17β-Estradiol (E2), acting via estrogen receptor (ER)-α, inhibits feeding in animals. One mechanism apparently involves an increase in the satiating potency of cholecystokinin (CCK) released from the small intestine by ingested food. For example, the satiating potency of intraduodenal lipid infusions is increased by E2 in ovariectomized rats; this increased satiation is dependent on CCK, and it is accompanied by increases in the numbers of ERα-positive cells that express c-Fos in a subregion of the caudal nucleus tractus solitarius (cNTS) that receives abdominal vagal afferent projections. To test whether direct administration of E2 to this area of the hindbrain is sufficient to inhibit food intake, we first implanted 0.2 μg estradiol benzoate (EB) in cholesterol or cholesterol alone either sc or onto the surface of the hindbrain over the cNTS. Food intake was significantly reduced after hindbrain EB implants but not after sc EB implants. Next we verified that equimolar hindbrain implants of E2 and EB had similar feeding-inhibitory effects and determined that only small amounts of E2 reached brain areas outside the dorsal caudal hindbrain after hindbrain implants of 3H-labeled E2. Neither plasma estradiol concentration nor plasma inflammatory cytokine concentration was increased by either hindbrain or sc EB implants. Finally, hindbrain EB implants, but not sc implants, increased c-Fos in ERα-positive cells in the cNTS after ip injection of 4 μg/kg CCK-8. We conclude that E2, acting via ERα in cNTS neurons, including neurons stimulated by ip CCK, is sufficient to inhibit feeding.

Electrophysiological evidence that systemic angiotensin influences rat area postrema neurons

1990 ◽  
Vol 258 (1) ◽  
pp. R70-R76 ◽  
Author(s):  
S. Papas ◽  
P. Smith ◽  
A. V. Ferguson
Keyword(s):  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Cell Types ◽  
Male Rats ◽  
Ang Ii ◽  
Adrenergic Agonist ◽  
Arterial Blood ◽  
Spontaneous Activities ◽  
Single Unit Recordings ◽  
Body Fluid Balance

Extracellular single-unit recordings from neurons in the area postrema (AP) and the nucleus tractus solitarius (NTS) in anesthetized male rats demonstrated that most cells in these regions have spontaneous activities of 5 Hz or less. Systemic angiotensin (ANG II) (50-500 ng) enhanced the activity of 55% of AP cells tested (n = 76), whereas 53% of tested NTS neurons (n = 62) were inhibited by ANG II. To determine whether these neurons were influenced specifically by circulating ANG II or by the accompanying increase in mean arterial blood pressure (BP), the effects of adrenergic agonists given intravenously on ANG II influenced neurons were also examined. Subsequently two cell types were characterized: cells responding to iv ANG II but not to the adrenergic agonist ("ANG II sensitive") and cells responding in a similar way to both agents ("BP sensitive"). Most ANG II-responsive neurons in the AP (53.5%) and the NTS (65%) were determined to be BP sensitive. These data demonstrate that ANG II influences the activity of AP neurons. In addition, there exists a second population of AP neurons apparently responsive to perturbations of the cardiovascular system. These studies further emphasize the potential roles of the AP in the regulation of body fluid balance.

scholarly journals Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α

2020 ◽  
Author(s):  
Shivani N. Mann ◽  
Niran Hadad ◽  
Molly Nelson-Holte ◽  
Alicia R. Rothman ◽  
Roshini Sathiaseelan ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Chronic Diseases ◽  
Transcriptional Activation ◽  
Estrogen Receptor Α ◽  
Metabolic Parameters ◽  
Metabolic Effects ◽  
Male Rats ◽  
Male Mice ◽  
Dietary Interventions ◽  
Estradiol Treatment

ABSTRACTMetabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice. The mechanisms by which 17α-estradiol elicits these benefits remain unresolved. Herein, we show that 17α-estradiol elicits similar genomic binding and transcriptional activation through estrogen receptor α (ERα) to that of 17β-estradiol. In addition, we show that the ablation of ERα completely attenuates the beneficial metabolic effects of 17α-E2 in male mice. Our findings suggest that 17α-E2 acts primarily through the liver and hypothalamus to improve metabolic parameters in male mice. Lastly, we also determined that 17α-E2 improves metabolic parameters in male rats, thereby proving that the beneficial effects of 17α-E2 are not limited to mice. Collectively, these studies suggest ERα may be a drug target for mitigating chronic diseases in male mammals.

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.

scholarly journals Estradiol Stimulates Apolipoprotein A-IV Gene Expression in the Nucleus of the Solitary Tract Through Estrogen Receptor-α

Endocrinology ◽  
2014 ◽  
Vol 155 (10) ◽  
pp. 3882-3890 ◽  
Author(s):  
Ling Shen ◽  
Yin Liu ◽  
David Q.H. Wang ◽  
Patrick Tso ◽  
Stephen C. Woods ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Nucleus Tractus Solitarius ◽  
Body Weight Gain ◽  
Gene Promoter ◽  
Estrogen Receptor Α ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Upstream Region ◽  
Apolipoprotein A

Abstract Although estrogens have been implicated in the regulation of apolipoprotein A-IV (apo A-IV) gene expression in the nucleus tractus solitarius, previous studies have not defined the molecular mechanism. The aim of this study was to examine the transcriptional mechanisms involved in regulation of apo A-IV gene expression. Using cultured primary neuronal cells from rat embryonic brainstems, we found that treatment with 10nM 17β-estradiol-3-benzoate (E2) or 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (an estrogen receptor [ER]α agonist), but not 2,3-bis(4-hydroxyphenyl)-propionitrile (an ERβ agonist), significantly increased apo A-IV gene expression, compared with vehicle treatment. This effect of E2 was abolished when the cells were incubated with E2 linked to BSA, which prevents E2 from entering cells, implying that a nongenomic mechanism of E2 is not involved. Two putative estrogen response elements were identified at the 5′-upstream region of the apo A-IV gene promoter, but only 1 of them was able to recruit ERα, leading to increased apo A-IV gene expression, as determined by chromatin immunoprecipitation assay and luciferase activity analysis. A cyclic regimen of E2 or 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol treatment for 8 cycles (4 d/cycle, mimicking the ovarian cycle of female rats) in ovariectomized female rats significantly reduced food intake and body weight gain and increased apo A-IV gene expression in the nucleus tractus solitarius, relative to vehicle. These data collectively demonstrate that nuclear ERα is the primary mediator of E2's action on apo A-IV gene expression and suggest that increased signaling of endogenous apo A-IV may at least partially mediate E2-induced inhibitory effect on feeding.

scholarly journals Leptin and the Control of Food Intake: Neurons in the Nucleus of the Solitary Tract Are Activated by Both Gastric Distension and Leptin

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2189-2197 ◽  
Author(s):  
Lihong Huo ◽  
Lisa Maeng ◽  
Christian Bjørbæk ◽  
Harvey J. Grill
Keyword(s):  
Food Intake ◽  
Nucleus Tractus Solitarius ◽  
Area Postrema ◽  
Significant Proportion ◽  
Gastric Distension ◽  
Reduce Food Intake ◽  
Signal Transducer ◽  
Electrophysiological Response ◽  
Fluorescent Immunohistochemistry ◽  
Transcription 3

Leptin reduces food intake by an unspecified mechanism. Studies show that forebrain ventricular leptin delivery increases the inhibitory effects of gastrointestinal (GI) stimulation on intake and amplifies the electrophysiological response to gastric distension in neurons of the medial subnucleus of the nucleus tractus solitarius (mNTS). However, forebrain ventricular delivery leaves unspecified the neuroanatomical site(s) mediating leptin’s effect on intake. Detailed anatomical analysis in rats and mice by phosphorylated signal transducer and activator of transcription 3 immunohistochemistry shows that hindbrain leptin-responsive neurons are located exclusively within the mNTS. Here, we investigate 1) whether leptin and gastric distension affect the same mNTS neurons and 2) whether the intake-inhibitory action of gastric distension is potentiated by hindbrain leptin delivery. Twenty-five minutes after gastric balloon distension or sham distension, rats were injected with leptin or vehicle and killed 35 min later. Double-fluorescent immunohistochemistry for phosphorylated signal transducer and activator of transcription 3 and c-Fos revealed that about 40% of leptin-responsive cells also respond to gastric distension. A paradigm was then developed to examine the relationship between leptin and gastric distension volume on intake inhibition. At subthreshold levels, hindbrain ventricular leptin or distension volume were without effect. When combined, an interaction occurred that significantly reduced food intake. We conclude that 1) leptin-responsive neurons in the hindbrain are primarily located in the mNTS at the level of the area postrema, a key vagal afferent projection zone of the GI system; 2) a significant proportion of leptin-responsive neurons in the mNTS are activated by stomach distension; and 3) leptin delivered to the hindbrain is sufficient to potentiate the intake-suppressive effects of an otherwise ineffective volume of gastric distension. These results are consistent with the hypothesis that leptin acts directly on neurons within the mNTS to reduce food intake through an interaction with GI signal processing.

scholarly journals Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Shivani N Mann ◽  
Niran Hadad ◽  
Molly Nelson Holte ◽  
Alicia R Rothman ◽  
Roshini Sathiaseelan ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Chronic Diseases ◽  
Transcriptional Activation ◽  
Estrogen Receptor Α ◽  
Metabolic Parameters ◽  
Metabolic Effects ◽  
Male Rats ◽  
Male Mice ◽  
Dietary Interventions ◽  
Estradiol Treatment

Metabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice. The mechanisms by which 17α-estradiol elicits these benefits remain unresolved. Herein, we show that 17α-estradiol elicits similar genomic binding and transcriptional activation through estrogen receptor α (ERα) to that of 17β-estradiol. In addition, we show that the ablation of ERα completely attenuates the beneficial metabolic effects of 17α-E2 in male mice. Our findings suggest that 17α-E2 may act through the liver and hypothalamus to improve metabolic parameters in male mice. Lastly, we also determined that 17α-E2 improves metabolic parameters in male rats, thereby proving that the beneficial effects of 17α-E2 are not limited to mice. Collectively, these studies suggest ERα may be a drug target for mitigating chronic diseases in male mammals.

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