Biomedical subjects

Rodrigo P A Barros

Publications and source records attributed to Rodrigo P A Barros.

4 recordsLinked to original sources

PubMed2006

Role of estrogen receptor beta in uterine stroma and epithelium: Insights from estrogen receptor beta-/- mice.

In this study, we compared the uterine tissue of estrogen receptor (ER)beta(-/-) 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 ERbeta(-/-) mice, but E-cadherin and cytokeratin 18 expression was lower in ERbeta(-/-) mice. The percentage of cells in S phase was 1.5% in WT mice and 8% in ERbeta(-/-) mice. Sixteen hours after injection of 17beta-estradiol (E(2)), the number of BrdUrd-labeled cells increased 20-fold in WT mice and 80-fold in ERbeta(-/-) mice. Although ERalpha was abundant in intact mice, after ovariectomy, ERalpha could not be detected in the luminal epithelium of either WT or ERbeta(-/-) mice. In both untreated and E(2)-treated mice, ERalpha and ERbeta were colocalized in the nuclei of many stromal and glandular epithelial cells. However, upon E(2) + progesterone treatment, ERalpha and ERbeta 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 ERbeta(-/-) mice, there was a marked expression of EGFR in the nuclei of epithelial and stromal cells. Upon E(2) treatment, EGFR on cell membranes was down-regulated in WT but not in ERbeta(-/-) mice. These findings reveal an important role for ERbeta in response to E(2) and in the organization, growth, and differentiation of the uterine epithelium.

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PubMed2006

Estrogen receptors: new players in diabetes mellitus.

Diabetes mellitus type 2 is a systemic disease characterized by imbalance of energy metabolism, which is mainly caused by inadequate insulin action. Recent data have revealed a surprising role for estradiol in regulating energy metabolism and opened new insights into the role of the two estrogen receptors, ERalpha and ERbeta, in this context. New findings on gene modulation by ERalpha and ERbeta of insulin-sensitive tissues indicate that estradiol participates in glucose homeostasis by modulating the expression of genes that are involved in insulin sensitivity and glucose uptake. Drugs that can selectively modulate the activity of either ERalpha or ERbeta in their interactions with target genes represent a promising frontier in diabetes mellitus coadjuvant therapy.

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PubMed2006

Lung dysfunction causes systemic hypoxia in estrogen receptor beta knockout (ERbeta-/-) mice.

Estrogen receptor beta (ERbeta) is highly expressed in both type I and II pneumocytes as well as bronchiolar epithelial cells. ERalpha is not detectable in the adult lung. Lungs of adult female ERbeta knockout (ERbeta-/-) mice have already been reported to have fewer alveoli and reduced elastic recoil. In this article, we report that, by 5 months of age, there are large areas of unexpanded alveoli in lungs of both male and female ERbeta-/- mice. There is increased staining for collagen and, by EM, abnormal clusters of collagen fibers are seen in the alveolar septa of ERbeta-/- mice. Immunohistochemical analysis and Western blotting with lung membrane fractions of ERbeta-/- mice revealed down-regulation of caveolin-1, increased expression of membrane type-1 metalloproteinase, matrix metalloproteinase 2 (active form), and tissue inhibitors of metalloproteinases 2. Hypoxia, measured by immunohistochemical analysis for hypoxia-inducible factor 1alpha and chemical adducts (with Hypoxyprobe), was evident in the heart, ventral prostate, periovarian sac, kidney, liver, and brain of ERbeta-/- mice under resting conditions. Furthermore, both male and female adult ERbeta-/- mice were reluctant to run on a treadmill and tissue hypoxia became very pronounced after exercise. We conclude that ERbeta is necessary for the maintenance of the extracellular matrix composition in the lung and loss of ERbeta leads to abnormal lung structure and systemic hypoxia. Systemic hypoxia may be responsible for the reported left and right heart ventricular hypertrophy and systemic hypertension in ERbeta-/- mice.

Animals↗

PubMed2006

Muscle GLUT4 regulation by estrogen receptors ERbeta and ERalpha.

Estrogen is known to influence glucose homeostasis with dominant effects in the liver, but the role of estrogen receptors in muscle glucose metabolism is unknown. In the present study, we investigated the expression of the two estrogen receptors, ERalpha and ERbeta, and their influence on regulation of the glucose transporter, GLUT4, and its associated structural protein, caveolin-1, in mouse gastrocnemius muscle. Immunohistochemical analysis revealed that ERalpha and ERbeta are coexpressed in the nuclei of most muscle cells, and that their levels were not affected by absence of estradiol [in aromatase-knockout (ArKO) mice]. GLUT4 expression on the muscle cell membrane was not affected by loss of ERbeta but was extremely reduced in ERalpha(-/-) mice and elevated in ArKO mice. RT-PCR confirmed a parallel reduction in GLUT4 mRNA levels in ERalpha(-/-) mice. Upon treatment of ArKO mice with the ERbeta agonist 2,3-bis(4-hydroxyphenyl)propionitrile, GLUT4 expression was reduced. By immunofluorescence and Western blotting, caveolin-1 expression was higher in ArKO mice and lower in ERbeta(-/-) and ERalpha(-/-) mice than in WT littermates. GLUT4 and caveolin-1 were colocalized in WT and ArKO mice but not in ERbeta(-/-) and ERalpha(-/-) mice. These results reveal that ERalpha is a positive regulator of GLUT4 expression, whereas ERbeta has a suppressive role. Both ERbeta and ERalpha are necessary for optimal caveolin-1 expression. Taken together, these results indicate that colocalization of caveolin-1 and GLUT4 is not an absolute requirement for muscle glucose metabolism but that reduction in GLUT4 could be contributing to the insulin resistance observed in ERalpha(-/-) mice.

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