Gender-Specific Alteration of Adrenergic Responses in Small Femoral Arteries From Estrogen Receptor-β Knockout Mice

Luksha, Leonid; Poston, Lucilla; Gustafsson, Jan Åke; Aghajanova, Lusine; Kublickiene, Karolina

doi:10.1161/01.hyp.0000185648.48498.c1

Cited by 26 publications

(24 citation statements)

References 48 publications

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“…In the WT, these arteries similarly express ER-␣ and ER-␤, as detected and reported by our group recently, and ER-␤ is absent in these arteries from the ␤-ERKO mice (30). The choice of vasculature was also supported by studies in femoral arteries from rats in which dilatory responses to estrogens were sex specific and, at least in part, NO mediated (51).…”

supporting

confidence: 74%

Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-β knockout mice

Cruz¹,

Douglas

Gustafsson

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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The objectives of this study were to determine whether acute dilatory responses to estrogen receptor agonists are altered in isolated arteries from estrogen receptor beta-deficient mice (beta-ERKO) and to gain insight into the role of nitric oxide (NO) in these responses. Femoral arteries (approximately 250 microm) from male and female beta-ERKO mice and wild-type (WT) littermates (26 female, 13 in each group; and 24 male, 12 in each group) were mounted on a Multi-Myograph. Concentration-response curves to 17beta-estradiol (17beta-E2) and the selective estrogen receptor-alpha (ER-alpha) agonist propyl-[1H]-pyrazole-1,3,5-triy-trisphenol (PPT) were obtained before and after NO synthase (NOS) inhibition [Nomega-nitro-L-arginine methyl ester (L-NAME), 0.1 mM] in arteries preconstricted with U-46619 (a thromboxane analog). In WT mice, responses to the potent estrogen receptor-beta (ER-beta) agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and the contribution of NO were also assessed. Concentration-response curves to 17beta-E2 and PPT were similar in arteries from WT and -ERKO mice of both genders, but NO-mediated relaxation was different, since L-NAME reduced 17-E2 mediated relaxation in arteries from male and female beta-ERKO but not WT mice (P < 0.05). NOS inhibition reduced dilation to PPT in arteries from male and female WT mice, as well as arteries from female beta-ERKO mice (P < 0.05). Responses to DPN in arteries from WT female and male mice did not differ after NOS inhibition. The acute dilatory responses to estrogenic compounds are similar in WT and beta-ERKO mice but differ mechanistically. Because NO appeared to contribute to responses to 17beta-E2 in arteries from beta-ERKO but not WT mice, the presence of ER- apparently inhibits ER--mediated NO relaxation.

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supporting

confidence: 74%

Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-β knockout mice

Cruz¹,

Douglas

Gustafsson

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Previous studies (7,12,22,30,34) have identified both ER subtypes in vascular endothelium and smooth muscle in a wide range of blood vessels in different vascular beds and from different species. In this study, the dilatory actions of PPT, a selective ER␣ agonist, and genistein, a predominant ER␤ agonist, were enhanced compared with those to 17␤-E 2 , a mixed agonist, or to resveratrol.…”

Section: Discussionmentioning

confidence: 99%

“…Each artery was mounted as an isometric preparation on stainless steel wires (diameter, 40 m) attached to a force transducer and a micrometer, respectively, as described previously (16,34). Commercially available software was used for calibrations and for data collection (Myodac, version 2.1, Danish Myo Technology).…”

Section: Patients Populationmentioning

confidence: 99%

Acute responses to phytoestrogens in small arteries from men with coronary heart disease

Cruz¹,

Luksha²,

Henareh³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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The aim of this study was to investigate acute vasodilator responses to phytoestrogens and selective estrogen receptor-alpha (ERalpha) agonist in isolated small arteries from men with established coronary heart disease (CHD) and with a history of myocardial infarction versus healthy male control subjects. As to methodology, small arteries obtained from subcutaneous fat biopsies and mounted on a wire myograph were preconstricted with norepinephrine, and dilator responses to increasing nanomolar-micromolar concentrations of the phytoestrogens resveratrol and genistein (predominantly ERbeta agonists) and to propyl-[1H]-pyrazole-1,3,5-triyl-trisplenol (PPT, a selective ERalpha agonist) were determined. These were compared with responses to reference compound 17beta-estradiol (17beta-E2). Concentration-response curves were constructed before and after nitric oxide (NO) synthase inhibition with Nomega-nitro-L-arginine methyl ester. As a result, relaxation induced by the investigated compounds was similar in men with CHD and control men, but in both groups PPT and genistein-induced relaxation was greater than that of resveratrol and 17beta-E2. NO contributed to both phytoestrogens and PPT-induced relaxation but not to 17beta-E2 responses in arteries from control men. This NO-mediated component of relaxation was absent in arteries from men with established CHD. In conclusion, phytoestrogens, at concentrations achievable by ingestion of phytoestrogen-rich food products, evoke dilatation ex vivo of small peripheral arteries from normal men and those with established CHD. The contribution of NO to dilatory responses by these compounds is pertinent to arteries from control males, whereas other NO-independent dilatory mechanism(s) are involved in arteries from CHD.

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“…As they age, male ER␤Ϫ/Ϫ mice develop hypertension due to abnormal adrenergic regulation of small artery tone (24). One of the consequences of hypertension is reduction in insulin-stimulated blood flow in SM (22).…”

Section: Discussionmentioning

confidence: 99%

Participation of ERα and ERβ in glucose homeostasis in skeletal muscle and white adipose tissue

Barros

Gabbi

Morani

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

131

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Glucose uptake and homeostasis are regulated mainly by skeletal muscle (SM), white adipose tissue (WAT), pancreas, and the liver. Participation of estradiol in this regulation is still under intense investigation. We have demonstrated that, in SM of male mice, expression of the insulinregulated glucose transporter (GLUT)4 is reduced by estrogen receptor (ER)␤ agonists. In the present study, to investigate the relative contributions of ER␣ and ER␤ in glucose homeostasis, we examined the effects of tamoxifen (Tam) on GLUT4 expression in SM and WAT in wild-type (WT) and ERϪ/Ϫ mice. ER␤Ϫ/Ϫ mice were characterized by fasting hypoglycemia, increased levels of SM GLUT4, pancreatic islet hypertrophy, and a belated rise in plasma insulin in response to a glucose challenge. ER␣Ϫ/Ϫ mice, on the contrary, were hyperglycemic and glucose intolerant, and expression of SM GLUT4 was markedly lower than in WT mice. Tam had no effect on glucose tolerance or insulin sensitivity in WT mice. In ER␣Ϫ/Ϫ mice, Tam increased GLUT4 and improved insulin sensitivity. i.e., it behaved as an ER␤ antagonist in SM but had no effect on WAT. In ER␤Ϫ/Ϫ mice, Tam did not affect GLUT4 in SM but acted as an ER␣ antagonist in WAT, decreasing GLUT4. Thus, in the interplay between ER␣ and ER␤, ER␤-mediated repression of GLUT4 predominates in SM but ER␣-mediated induction of GLUT4 predominates in WAT. This tissue-specific difference in dominance of one ER over the other is reflected in the ratio of the expression of the two receptors. ER␣ predominates in WAT and ER␤ in SM.estrogen receptor-␣; estrogen receptor-␤; glucose transporter 4; tamoxifen FOR SEVERAL DECADES the multiple and sometimes contradictory effects of estrogens on human physiology and disease have puzzled endocrinologists. Even today, the modulatory effects of estrogen on glucose homeostasis are not completely understood. The effects of estrogen on gene regulation are mediated by two sometimes opposing forces, estrogen receptor (ER)␣ and ER␤ (20, 28), in both females and males (19,25). Recent experimental evidence has revealed that estradiol (E 2 ) is an important modulator in tissues previously not considered to be classical estrogen targets.In mice, insulin resistance develops when there is no estrogen (in aromatase-knockout mice) and when ER␣ is inactivated (ER␣Ϫ/Ϫ mice) (5,17,19). In women, a clear relationship between E 2 and glycemia has been observed during the menstrual cycle (32), in gestation (7), in gestational diabetes mellitus, and in polycystic ovarian syndrome (11). In normal males, because of the absence of estrogen cyclicity, the effect of estrogen on glycemia is less obvious, but men with hypoestrogenism or with mutations in the aromatase (13) or ER␣ (31) genes do develop insulin resistance.Insulin is the most important hormone for the maintenance of euglycemia. It regulates carbohydrate metabolism in the liver and glucose uptake in insulin-sensitive tissues, i.e., skeletal muscle (SM) and white adipose tissue (WAT) (12). On binding to its receptors on the cell membrane o...

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Gender-Specific Alteration of Adrenergic Responses in Small Femoral Arteries From Estrogen Receptor-β Knockout Mice

Cited by 26 publications

References 48 publications

Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-β knockout mice

Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-β knockout mice

Acute responses to phytoestrogens in small arteries from men with coronary heart disease

Participation of ERα and ERβ in glucose homeostasis in skeletal muscle and white adipose tissue

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