Muscle GLUT4 regulation by estrogen receptors ERβ and ERα

Barros, Rodrigo P.A.; Machado, Ubiratan Fabres; Warner, Margaret; Gustafsson, Jan‐Åke

doi:10.1073/pnas.0510391103

Cited by 237 publications

(207 citation statements)

References 29 publications

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“…ER␣ and ER␤ were detected in tissue sections by standard immunofluorescence as described in ref. 42. For immunofluorescent detection, 4-m paraffin sections were dewaxed in xylene and rehydrated through graded ethanol to water.…”

Section: Methodsmentioning

confidence: 99%

Role of estrogen receptor β in uterine stroma and epithelium: Insights from estrogen receptor β ^−/− mice

Wada-Hiraike

Hiraike

Okinaga

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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105

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In this study, we compared the uterine tissue of estrogen receptor (ER)␤ ؊/؊ mice and their WT littermates for differences in morphology, proliferation [the percentage of labeled cells 2 h after BrdUrd injection and EGF receptor (EGFR) expression], and differentiation (expression of progesterone receptor, E-cadherin, and cytokeratins). In ovariectomized mice, progesterone receptor expression in the uterine epithelium was similar in WT and ER␤ ؊/؊ mice, but E-cadherin and cytokeratin 18 expression was lower in ER␤ ؊/؊ mice. The percentage of cells in S phase was 1.5% in WT mice and 8% in ER␤ ؊/؊ mice. Sixteen hours after injection of 17␤-estradiol (E2), the number of BrdUrd-labeled cells increased 20-fold in WT mice and 80-fold in ER␤ ؊/؊ mice. Although ER␣ was abundant in intact mice, after ovariectomy, ER␣ could not be detected in the luminal epithelium of either WT or ER␤ ؊/؊ mice. In both untreated and E2-treated mice, ER␣ and ER␤ were colocalized in the nuclei of many stromal and glandular epithelial cells. However, upon E2 ؉ progesterone treatment, ER␣ and ER␤ were not coexpressed in any cells. In WT mice, EGFR was located on the membranes and in the cytoplasm of luminal epithelium, but not in the stroma. In ER␤ ؊/؊ mice, there was a marked expression of EGFR in the nuclei of epithelial and stromal cells. Upon E2 treatment, EGFR on cell membranes was down-regulated in WT but not in ER␤ ؊/؊ mice. These findings reveal an important role for ER␤ in response to E2 and in the organization, growth, and differentiation of the uterine epithelium.differentiation ͉ proliferation ͉ uterus P roliferation of epithelial cells (1, 2), uterine hyperemia, fluid uptake (termed water imbibition), recruitment of inflammatory leukocytes from the bloodstream into the stromal compartment (3, 4), and the induction of the progesterone receptor (PR) are caused by 17␤-estradiol (E 2 ). Progesterone (P 4 ) inhibits estrogen-induced cell proliferation of the luminal and glandular epithelial compartment (5) and stimulates epithelial differentiation in preparation for embryo implantation. Physiologically and pharmacologically, P 4 is important for prevention of endometrial hyperplasia (6). After the cessation of ovarian function, estrogen replacement is needed for preservation of the skeletal, cardiovascular, and central nervous systems. To oppose the proliferative effects of estrogen on the uterus and reduce the risk of endometrial cancer, progesterone is used together with estrogen in hormone replacement therapy after menopause (7,8).Most of the known actions of estrogen are mediated by the estrogen receptors (ERs) ER␣ and ER␤, both of which bind E 2 and modulate transcription of E 2 -responsive genes (9). A single injection of E 2 results in a synchronized wave of cell proliferation, with DNA synthesis in epithelial cells beginning 6-9 h after E 2 injection and peaking at 12-15 h. DNA synthesis is followed by a wave of cell division (1, 2, 10). P 4 elicits its function through binding to the PR.During the secretory phase of the estrus...

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Section: Methodsmentioning

confidence: 99%

Role of estrogen receptor β in uterine stroma and epithelium: Insights from estrogen receptor β ^−/− mice

Wada-Hiraike

Hiraike

Okinaga

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

105

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“…Pellets were dissolved in SDS sample buffer, and the proteins were resolved by SDSpolyacrylamide gel electrophoresis with 4-20% gradient gels (Invitrogen, Carlsbad, CA, USA) as described before. 42,43 After transfer to PVDF membranes (Applied Biosystems, Foster City, CA, USA), blots were probed with anti-ERbLBD antibody, followed by appropriate secondary antibodies conjugated with horseradish peroxidase. Detection was by enhanced chemiluminescence ECL kit (Amersham Pharmacia, Pittsburgh, PA, USA).…”

Section: Western Blottingmentioning

confidence: 99%

Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

Sugiyama

Andersson

Lathe³

et al. 2008

Mol Psychiatry

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This study reports on the spatiotemporal dynamics of the expression of estrogen receptors (ERs) in the mouse central nervous system (CNS) during the early postnatal and the peripubertal period. At postnatal day 7 (P7), neurons with strong nuclear immunostaining for both ERa and ERb1 were widely distributed throughout the brain. Sucrose density gradient sedimentation followed by western blotting supported the histochemical evidence for high levels of both ERs at P7. Over the following 2 days, there was a rapid downregulation of ERs. At P9, ERa expression was visible only in the hypothalamic area. Decline in ERb1 expression was slower than that of ERa, and ERa-negative, ERb1-positive cells were observed in the dentate gyrus and walls of third ventricle. Between P14 and P35, ERs were undetectable except for the hypothalamic area. As before P7, the ovary does not produce estrogen but does produce 5a-androstane-3b, 17b-diol (3bAdiol), an estrogenic metabolite of dihydrotestosterone, we examined the effects of high levels of 3bAdiol in the postnatal period. We used CYP7B1 knockout mice which cannot hydroxylate and inactivate 3bAdiol. The brains of these mice are abnormally large with reduced apoptosis. In the early postnatal period, there was 1-week delay in the timing of the reduction in ER expression in the brain. These data reveal that the time when ERs might be activated in the brain is limited to the first 8 postnatal days. In addition, the importance of aromatase has to be reconsidered as the alternative estrogen, 3bAdiol, is important in neuronal function in the postnatal brain.

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“…In women with gestational diabetes mellitus, however, the problem regarding tissue insulin sensitivity is restricted to post-binding steps, such as reduced tyrosine kinase activity, decreased expression of insulin receptor substrate-1 (IRS-1) and increased levels of the p85α subunit of PI 3-kinase (Barbour et al 2007). Interestingly, estrogens have been implicated in changes in insulin secretion, and also in reduced insulin sensitivity and glucose tolerance, especially in muscles (Godsland 2005, Barros et al 2006. Batista et al (2005) showed that chronic exposure of bitches to estradiol and progesterone causes insulin resistance in the whole body, but primarily in the skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

Insulin binding characteristics in canine muscle tissue: effects of the estrous cycle phases

et al. 2016

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Hormonal fluctuations during the different estrous cycle are a well-recognized cause of insulin resistance in bitches, and little is known about insulin receptor binding or post-binding defects associated with insulin resistance in dogs. To evaluate insulin binding characteristics in muscle tissue of bitches during the estrous cycle, 17 owned bitches were used in the study (six in anestrus, five in estrus, and six in diestrus). An intravenous glucose tolerance test (IVGTT) was performed in all patients by means of injection of 1mL/kg of a glucose 50% solution (500mg/kg), with blood sample collection for glucose determination at 0, 3, 5, 7, 15, 30, 45 and 60 minutes after glucose infusion. Muscle samples, taken after spaying surgery, were immediately frozen in liquid nitrogen and then stored at -80 ºC until the membranes were prepared by sequential centrifugation after being homogenized. For binding studies, membranes were incubated in the presence of 20,000cpm of human 125I-insulin and in increasing concentrations of unlabeled human regular insulin for cold saturation. The IVGTT showed no differences among bitches during the estrous cycle regarding baseline glycemia or glycemic response after glucose infusion. Two insulin binding sites - high-affinity and low-affinity ones - were detected by Scatchard analysis, and significant statistical differences were observed in the dissociation constant (Kd1) and maximum binding capacity (Bmax1) of the high-affinity binding sites. The Kd1 for the anestrus group (6.54±2.77nM/mg of protein) was smaller (P<0.001) than for the estrus (28.54±6.94nM/mg of protein) and diestrus (15.56±3.88nM/mg of protein) groups. Bmax1 in the estrus (0.83±0.42nM/mg of protein) and diestrus (1.24±0.24nM/mg of protein) groups were also higher (P<0.001) than the values observed in anestrus (0.35±0.06nM/mg of protein). These results indicate modulation of insulin binding characteristics during different phases of the estrous cycle in dogs, showing that muscle insulin binding affinity for its receptor is reduced during estrus and diestrus. However, this poor hormone-receptor affinity is compensated for by a greater total binding capacity, once there is no difference in patients' glycemic response after an intravenous glucose load.

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Muscle GLUT4 regulation by estrogen receptors ERβ and ERα

Cited by 237 publications

References 29 publications

Role of estrogen receptor β in uterine stroma and epithelium: Insights from estrogen receptor β ^−/− mice

Role of estrogen receptor β in uterine stroma and epithelium: Insights from estrogen receptor β ^−/− mice

Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

Insulin binding characteristics in canine muscle tissue: effects of the estrous cycle phases

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Muscle GLUT4 regulation by estrogen receptors ERβ and ERα

Cited by 237 publications

References 29 publications

Role of estrogen receptor β in uterine stroma and epithelium: Insights from estrogen receptor β −/− mice

Role of estrogen receptor β in uterine stroma and epithelium: Insights from estrogen receptor β −/− mice

Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

Insulin binding characteristics in canine muscle tissue: effects of the estrous cycle phases

Contact Info

Product

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Role of estrogen receptor β in uterine stroma and epithelium: Insights from estrogen receptor β ^−/− mice

Role of estrogen receptor β in uterine stroma and epithelium: Insights from estrogen receptor β ^−/− mice