scholarly journals Estren Behaves as a Weak Estrogen Rather than a Nongenomic Selective Activator in the Mouse Uterus

Endocrinology ◽  
2006 ◽  
Vol 147 (5) ◽  
pp. 2203-2214 ◽  
Author(s):  
Sylvia C. Hewitt ◽  
Jennifer Collins ◽  
Sherry Grissom ◽  
Katherine Hamilton ◽  
Kenneth S. Korach
Keyword(s):  
Gene Expression ◽  
Maximal Response ◽  
Similar Response ◽  
Nuclear Fraction ◽  
Wild Type ◽  
Mouse Uterus ◽  
Cytosol Fraction ◽  
Ovariectomized Mice ◽  
Nuclear Estrogen Receptor ◽  
Induced Changes

A proposed membrane-mediated mechanism of rapid nongenomic response to estrogen has been the intense focus of recent research. Estren, a synthetic steroid, is reported to act selectively through a rapid membrane-mediated pathway, rather than through the classical nuclear estrogen receptor (ER)-mediated pathway, to maintain bone density in ovariectomized mice without uterotropic effects. To evaluate the mechanism and physiological effects of estren, we studied responses in adult ovariectomized mice. In a 3-d uterine bioassay, we found that 300 μg estren significantly increased uterine weight; in comparison, a more maximal response was seen with 1 μg estradiol (E2). The estren response was partly ERα independent, because ERα knockout (αERKO) uteri also exhibited a more moderate weight increase. Estren induced epithelial cell proliferation in wild-type, but not αERKO, mice, indicating ERα dependence of the epithelial growth response. Examination of estren-regulated uterine genes by microarray indicated that early (2 h) changes in gene expression are similar to the early responses to E2. These gene responses are ERα dependent, because they are not seen in αERKO mice. Later estren-induced changes in gene expression (24 h) are blunted compared with those seen 24 h after E2. In contrast to early genes, these later estren responses are independent of ERα, because the αERKO shows a similar response to estren at 24 h. We found that E2 or estren treatments lead to depletion of ERα in the uterine cytosol fraction and accumulation in the nuclear fraction within 30–60 min, consistent with the ability of estren to regulate genes through a nuclear ERα rather than a nongenomic mechanism. Interestingly, estren, but not E2, induces accumulation of androgen receptor (AR) in the nuclear fraction of both wild-type and αERKO samples, suggesting that AR might be involved in the later ERα-independent genomic responses to estren. In conclusion, our studies suggest that estren is weakly estrogenic in the mouse uterus and might induce nuclear ERα- and AR-mediated responses. Given its activity in our uterine model, the use of estren as a bone-selective clinical compound needs to be reconsidered.

scholarly journals Estradiol induces C-type natriuretic peptide gene expression in mouse uterus

1997 ◽  
Vol 273 (6) ◽  
pp. H2672-H2677 ◽  
Author(s):  
Cory G. Acuff ◽  
Huaming Huang ◽  
Mark E. Steinhelper
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Natriuretic Peptide ◽  
Actinomycin D ◽  
Mouse Uterus ◽  
Ovariectomized Mice ◽  
Nuclear Estrogen Receptor ◽  
Ribonuclease Protection ◽  
Peptide Gene ◽  
Maximal Expression

Previous experiments have demonstrated that C-type natriuretic peptide (CNP) expression in the uterus varies during the estrous cycle with maximal expression at proestrus. The present study was designed to determine whether exogenous steroid hormones regulate uterine CNP expression in ovariectomized mice. Estradiol increased significantly (3-fold) uterine immunoreactive CNP (irCNP) rapidly and dose dependently in ovariectomized mice as measured by radioimmunoassay. Other steroids produced either no significant change (testosterone, 1 mg; 2-methoxyestradiol, 1 μg) or weak induction (estriol, 1 μg) from vehicle controls. Progesterone (1 mg) significantly attenuated the estrogen-stimulated irCNP response by 50% when injected 30 min before estrogen (1 μg) in estrogen-primed ovariectomized mice. Estrogen-stimulated increases in uterine CNP transcripts detected by ribonuclease protection analyses were blocked by actinomycin D (160 μg) or ICI-164,384 (20 μg), a specific nuclear estrogen receptor antagonist. These results indicate that a nuclear estrogen receptor is required for estrogen to stimulate uterine CNP transcription and that progesterone negatively regulates estrogen-stimulated CNP expression.

High-fat diet-induced changes in body mass and hypothalamic gene expression in wild-type and leptin-deficient mice

Endocrine ◽  
2008 ◽  
Vol 33 (2) ◽  
pp. 176-188 ◽  
Author(s):  
Kristy L. Townsend ◽  
Magen M. Lorenzi ◽  
Eric P. Widmaier
Keyword(s):  
Gene Expression ◽  
Body Mass ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Induced Changes ◽  
Deficient Mice

scholarly journals Single cell RNA-seq study of wild type and Hox9,10,11 mutant developing uterus

2018 ◽  
Author(s):  
Michael L. Mucenski ◽  
Robert Mahoney ◽  
Mike Adam ◽  
Andrew S. Potter ◽  
S. Steven Potter
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Hox Genes ◽  
Expression Patterns ◽  
Wild Type Mouse ◽  
Cell Types ◽  
Specific Gene ◽  
Rna Seq ◽  
Wild Type ◽  
Mouse Uterus

AbstractThe uterus is a remarkable organ that must guard against infections while maintaining the ability to support growth of a fetus without rejection. The Hoxa10 and Hoxa11 genes have previously been shown to play essential roles in uterus development and function. In this report we show that the Hoxc9,10,11 genes play a redundant role in the formation of uterine glands. In addition, we use single cell RNA-seq to create a high resolution gene expression atlas of the developing wild type mouse uterus. Cell types and subtypes are defined, for example dividing endothelial cells into arterial, venous, capillary, and lymphatic, while epithelial cells separate into luminal and glandular subtypes. Further, a surprising heterogeneity of stromal and myocyte cell types are identified. Transcription factor codes and ligand/receptor interactions are characterized. We also used single cell RNA-seq to globally define the altered gene expression patterns in all developing uterus cell types for two Hox mutants, with 8 or 9 mutant Hox genes. The mutants show a striking disruption of Wnt signaling as well as the Cxcl12/Cxcr4 ligand/receptor axis.Summary statementA single cell RNA-seq study of the developing mouse uterus defines cellular heterogeneities, lineage specific gene expression programs and perturbed pathways in Hox9,10,11 mutants.

scholarly journals Secreted phosphoprotein 1 (osteopontin) is expressed by stromal macrophages in cyclic and pregnant endometrium of mice, but is induced by estrogen in luminal epithelium during conceptus attachment for implantation

Reproduction ◽  
2006 ◽  
Vol 132 (6) ◽  
pp. 919-929 ◽  
Author(s):  
Frankie J White ◽  
Robert C Burghardt ◽  
Jianbo Hu ◽  
Margaret M Joyce ◽  
Thomas E Spencer ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Immune Cells ◽  
Luminal Epithelium ◽  
Apical Surface ◽  
Wild Type ◽  
Mouse Uterus ◽  
Ovariectomized Mice ◽  
Vaginal Plug ◽  
Secreted Phosphoprotein 1

Secreted phosphoprotein 1 (SPP1, osteopontin) is the most highly upregulated extracellular matrix/adhesion molecule/cytokine in the receptive phase human uterus, and Spp1 null mice manifest decreased pregnancy rates during mid-gestation as compared with wild-type counterparts. We hypothesize that Spp1 is required for proliferation, migration, survival, adhesion, and remodeling of cells at the conceptus–maternal interface. Our objective was to define the temporal/spatial distribution and steroid regulation of Spp1 in mouse uterus during estrous cycle and early gestation.In situhybridization localizedSpp1to luminal epithelium (LE) and immune cells. LE expression was prominent at proestrus, decreased by estrus, and was nearly undetectable at diestrus. During pregnancy,Spp1mRNA was not detected in LE until day 4.5 (day 1 = vaginal plug).Spp1-expressing immune cells were scattered within the endometrial stroma throughout the estrous cycle and early pregnancy. Immunoreactive Spp1 was prominent at the apical LE surface by day 4.5 of pregnancy and Spp1 protein was also co-localized with subsets of CD45-positive (leukocytes) and F4/80-positive (macrophages) cells. In ovariectomized mice, estrogen, but not progesterone, inducedSpp1mRNA, whereas estrogen plus progesterone did not induceSpp1in LE. These results establish that estrogen regulates Spp1 in mouse LE and are the first to identify macrophages that produce Spp1 within the peri-implantation endometrium of any species. We suggest that Spp1 at the apical surface of LE provides a mechanism to bridge conceptus to LE during implantation, and that Spp1-positive macrophages within the stroma may be involved in uterine remodeling for conceptus invasion.

scholarly journals Identification of Murine Uterine Genes Regulated in a Ligand-Dependent Manner by the Progesterone Receptor

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3490-3505 ◽  
Author(s):  
Jae-Wook Jeong ◽  
Kevin Y. Lee ◽  
Inseok Kwak ◽  
Lisa D. White ◽  
Susan G. Hilsenbeck ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progesterone Receptor ◽  
Major Change ◽  
Dependent Manner ◽  
Wild Type ◽  
Mouse Uterus ◽  
Oligonucleotide Arrays ◽  
Metabolic Genes ◽  
Cytochrome P 450

Abstract Progesterone (P4) acting through its cognate receptor, the progesterone receptor (PR), plays an important role in uterine physiology. The PR knockout (PRKO) mouse has demonstrated the importance of the P4-PR axis in the regulation of uterine function. To define the molecular pathways regulated by P4-PR in the mouse uterus, Affymetrix MG U74Av2 oligonucleotide arrays were used to identify alterations in gene expression after acute and chronic P4 treatments. PRKO and wild-type mice were ovariectomized and then treated with vehicle or 1 mg P4 every 12 h. Mice were killed either 4 h after the first injection (acute P4 treatment) or after the fourth injection of P4 (chronic P4 treatment). At the genomic level, the major change in gene expression after acute P4 treatment was an increase in the expression of 55 genes. Conversely, the major change in gene expression after chronic P4 treatment was an overall reduction in the expression of 102 genes. In the analysis, retinoic acid metabolic genes, cytochrome P 450 26a1 (Cyp26a1), alcohol dehydrogenase 5, and aldehyde dehydrogenase 1a1 (Aldh1a1); kallikrein genes, Klk5 and Klk6; and specific transcription factors, GATA-2 and Cited2 [cAMP-corticosterone-binding protein/p300-interacting transactivator with glutamic acid (E) and aspartic acid (D)-rich tail], were validated as regulated by the P4-PR axis. Identification and analysis of these responsive genes will help define the role of PR in regulating uterine biology.

Microarray reveals positive effects of green and black tea polyphenols on TNF[alpha]-induced changes of gene expression

2013 ◽  
Author(s):  
Husna Zulkipli ◽  
Norita Salim ◽  
Gabriele Anisah Froemming ◽  
Aletza Mohd Ismail ◽  
Hapizah Nawawi
Keyword(s):  
Gene Expression ◽  
Black Tea ◽  
Tea Polyphenols ◽  
Tnf Alpha ◽  
Positive Effects ◽  
Black Tea Polyphenols ◽  
Green And Black Tea ◽  
Induced Changes

Methacholine-induced bronchoconstriction in dogs: effects of lung volume and O3 exposure

1988 ◽  
Vol 65 (6) ◽  
pp. 2679-2686 ◽  
Author(s):  
S. T. Kariya ◽  
S. A. Shore ◽  
W. A. Skornik ◽  
K. Anderson ◽  
R. H. Ingram ◽  
...  
Keyword(s):  
Lung Volume ◽  
Maximal Response ◽  
Maximal Effect ◽  
Response Curves ◽  
Lung Volumes ◽  
Before And After ◽  
Residual Capacity ◽  
Induced Changes ◽  
Conducting Airways ◽  
Concentration Response Curve

The maximal effect induced by methacholine (MCh) aerosols on pulmonary resistance (RL), and the effects of altering lung volume and O3 exposure on these induced changes in RL, was studied in five anesthetized and paralyzed dogs. RL was measured at functional residual capacity (FRC), and lung volumes above and below FRC, after exposure to MCh aerosols generated from solutions of 0.1-300 mg MCh/ml. The relative site of response was examined by magnifying parenchymal [RL with large tidal volume (VT) at fast frequency (RLLS)] or airway effects [RL with small VT at fast frequency (RLSF)]. Measurements were performed on dogs before and after 2 h of exposure to 3 ppm O3. MCh concentration-response curves for both RLLS and RLSF were sigmoid shaped. Alterations in mean lung volume did not alter RLLS; however, RLSF was larger below FRC than at higher lung volumes. Although O3 exposure resulted in small leftward shifts of the concentration-response curve for RLLS, the airway dominated index of RL (RLSF) was not altered by O3 exposure, nor was the maximal response using either index of RL. These data suggest O3 exposure does not affect MCh responses in conducting airways; rather, it affects responses of peripheral contractile elements to MCh, without changing their maximal response.

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