Characterization of the ERβ
            <sup>–</sup>
            /–mouse heart

Förster, Carola; Kietz, Silke; Hultenby, Kjell; Warner, Margaret; Gustafsson, Jan Åke

doi:10.1073/pnas.0405571101

Cited by 63 publications

(52 citation statements)

References 52 publications

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“…29,30 In contrast to previous studies, which failed to detect measurable amounts of ER␣ and ER␤ protein in the mouse heart, several independent studies reported on robust cardiac expression levels of both ER subtypes in rats and humans. 10,31,32 However, cardiac expression levels of ER␣ and ER␤ may not only vary between different species but also among young and senescent SHRs. Therefore, it is interesting to note that cardiac ER␣ expression was significantly lower in sham-operated and ovariectomized aged rats, whereas ER␤ was detected at comparable amounts in the heart of young and senescent rats.…”

Section: Discussionmentioning

confidence: 99%

Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

Jazbutyte

Kruchten

et al. 2006

Hypertension

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Abstract-Clinical trials failed to show a beneficial effect of postmenopausal hormone replacement therapy, whereas experimental studies in young animals reported a protective function of estrogen replacement in cardiovascular disease. Because these diverging results could in part be explained by aging effects, we compared the efficacy of estrogen substitution to modulate cardiac hypertrophy and cardiac gene expression among young (age 3 months) and senescent (age 24 months) spontaneously hypertensive rats (SHRs), which were sham operated or ovariectomized and injected with placebo or identical doses of 17␤-estradiol (E2; 2 g/kg body weight per day) for 6 weeks (nϭ10/group). Blood pressure was comparable among sham-operated senescent and young SHRs and not altered by ovariectomy or E2 treatment among young or among senescent rats. Estrogen substitution inhibited uterus atrophy and gain of body weight in young and senescent ovariectomized SHRs, but cardiac hypertrophy was attenuated only in young rats. Cardiac estrogen receptor-␣ expression was lower in intact and in ovariectomized senescent compared with young SHRs and increased with estradiol substitution in aged rats. Plasma estradiol and estrone levels were lower not only in sham-operated but surprisingly also in E2-substituted senescent SHRs and associated with a reduction of hepatic 17␤-hydroxysteroid dehydrogenase type 1 enzyme activity, which converts weak (ie, estrone) into potent estrogens, such as E2. Aging attenuates the antihypertrophic effect of estradiol in female SHRs and is associated with profound alterations in cardiac estrogen receptor-␣ expression and estradiol metabolism. These observations contribute to explain the lower efficiency of estrogen substitution in senescent SHRs. (Hypertension. 2006;48:579-586.)

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Section: Discussionmentioning

confidence: 99%

Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

Jazbutyte

Kruchten

et al. 2006

Hypertension

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“…3). ER expression, as measured by [ 3 H]E 2 binding, in breast tumors ranges between 10-1000 fmol/mg nuclear protein (0.01-1fmol/mg) and 2-3 pmol/mg (2-3 fmol/mg) cytosolic protein (Forster et al 2004 Our results in lung adenocarcinoma differ from breast cancer where progression to estrogen independence and anti-estrogen resistance is often associated with decreased ERa expression (Yang et al 2001); the results also differ from endometrial and ovarian cancer where the ERb : ERa ratio is decreased compared with the respective non-cancer tissues (Pujol et al 1998, Fujimoto et al 2000, Li et al 2003. Moreover, E 2 binding was higher in NEs compared with CEs, indicating that sequestration of ER outside the nucleus does not appear to be the cause of the lack of ER responses in the adenocarcinoma cells from males.…”

Section: Discussionmentioning

confidence: 99%

Gender difference in the activity but not expression of estrogen receptors α and β in human lung adenocarcinoma cells

Dougherty¹,

Mazhawidza²,

Bohn³

et al. 2006

Endocr Relat Cancer

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The higher frequency of lung adenocarcinoma in women smokers than in men smokers suggests a role for gender-dependent factors in the etiology of lung cancer. We evaluated estrogen receptor (ER) a and b expression and activity in human lung adenocarcinoma cell lines and normal lung fibroblasts. Full-length ERa and ERb proteins were expressed in all cell lines with higher ERb than ERa. Although estradiol (E 2 ) binding was similar, E 2 stimulated proliferation only in cells from females, and this response was inhibited by anti-estrogens 4-hydroxytamoxifen (4-OHT) and ICI 182,780. In contrast, E 2 did not stimulate replication of lung adenocarcinoma cells from males and 4-OHT or ICI did not block cell proliferation. Similarly, transcription of an estrogen response element-driven reporter gene was stimulated by E 2 in lung adenocarcinoma cells from females, but not males. Progesterone receptor (PR) expression was increased by E 2 in two out of five adenocarcinoma cell lines from females, but none from males. E 2 decreased E-cadherin protein expression in some of the cell lines from females, as it did in MCF-7 breast cancer cells, but not in the cell lines from males. Thus, ERa and ERb expression does not correlate with the effect of ER ligands on cellular activities in lung adenocarcinoma cells. On the other hand, coactivator DRIP205 expression was higher in lung adenocarcinoma cells from females versus males and higher in adenocarcinoma cells than in normal human bronchial epithelial cells. DRIP205 and other ER coregulators may contribute to differences in estrogen responsiveness between lung adenocarcinoma cells in females and males.

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“…ER is the more expressed receptor in central nervous and cardiovascular systems, and prostate gland, whereas ER plays a dominant role in mammary gland and uterus (Couse et al 1997, Forster et al 2004. ER is believed to play a central role in the origin and progression of breast cancer; however, recent studies suggest that ER can suppress breast cancer progression (Paruthiyil et al 2004, Strom et al 2004.…”

Section: Thermal Unfolding and Conformational Dynamics Of Er And Er ·mentioning

confidence: 99%

Conformational dynamics of estrogen receptors α and β as revealed by intrinsic tryptophan fluorescence and circular dichroism

Nair¹,

Greenfield²,

Chen³

et al. 2005

Journal of Molecular Endocrinology

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Estrogen receptors (ER and ER ) are ligand-activated nuclear receptors that mediate the action of estrogens. These receptors activate transcription by similar mechanism(s), although the overall amino acid sequence identity is only 47%. In order to compare the structural and conformational features of ER and ER , we monitored their intrinsic tryptophan fluorescence during thermal unfolding. The 50% unfolding temperatures (T M ) of ER and ER were 39±1 and 40±2°C, respectively. Estradiol had no significant effect on the T M of ER or ER . In contrast, binding of the estrogen-response element increased the T M of ER and ER by 10°C. Thermal unfolding of estradiol-bound ER and ligand-free ER showed two-step transitions, with the formation of intermediates that were stable between 36-48 and 34-42°C, respectively. We confirmed the presence of intermediate states during thermal unfolding by circular dichroism spectroscopy. Atomic force microscopy showed that the ER intermediate consisted of discrete globular particles, whereas the ER intermediate showed a speckled appearance, with sparse well-defined particles. Fluorescence-quenching studies showed the presence of two classes of tryptophan in unliganded ER and ER . Binding of estradiol to ER exposed its tryptophans, whereas estradiol reduced the accessibility of the tryptophans of ER . Our results illustrate the differential effects of ligands on the unfolding of ER and ER , and identify partially unfolded intermediates. Differences in the conformational flexibility and stability of ER and ER may represent functional differences of ligand-bound ERs in recruiting coactivator proteins and initiating transcription.

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Characterization of the ERβ ^– /–mouse heart

Cited by 63 publications

References 52 publications

Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

Gender difference in the activity but not expression of estrogen receptors α and β in human lung adenocarcinoma cells

Conformational dynamics of estrogen receptors α and β as revealed by intrinsic tryptophan fluorescence and circular dichroism

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Characterization of the ERβ – /–mouse heart

Cited by 63 publications

References 52 publications

Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

Gender difference in the activity but not expression of estrogen receptors α and β in human lung adenocarcinoma cells

Conformational dynamics of estrogen receptors α and β as revealed by intrinsic tryptophan fluorescence and circular dichroism

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Characterization of the ERβ ^– /–mouse heart