scholarly journals Wilms' Tumor Protein Wt1 Is an Activator of the Anti-Müllerian Hormone Receptor Gene Amhr2

2007 ◽  
Vol 27 (12) ◽  
pp. 4355-4364 ◽  
Author(s):  
Jürgen Klattig ◽  
Ralph Sierig ◽  
Dagmar Kruspe ◽  
Birgit Besenbeck ◽  
Christoph Englert

ABSTRACT The Wilms' tumor protein Wt1 plays an essential role in mammalian urogenital development. WT1 mutations in humans lead to a variety of disorders, including Wilms' tumor, a pediatric kidney cancer, as well as Frasier and Denys-Drash syndromes. Phenotypic anomalies in Denys-Drash syndrome include pseudohermaphroditism and sex reversal in extreme cases. We have used cDNA microarray analyses on Wt1 knockout mice to identify Wt1-dependent genes involved in sexual development. The gene most dramatically affected by Wt1 inactivation was Amhr2, encoding the anti-Müllerian hormone (Amh) receptor 2. Amhr2 is an essential factor for the regression of the Müllerian duct in males, and mutations in AMHR2 lead to the persistent Müllerian duct syndrome, a rare form of male pseudohermaphroditism. Here we show that Wt1 and Amhr2 are coexpressed during urogenital development and that the Wt1 protein binds to the promoter region of the Amhr2 gene. Inactivation and overexpression of Wt1 in cell lines was followed by immediate changes of Amhr2 expression. The identification of Amhr2 as a Wt1 target provides new insights into the role of Wt1 in sexual differentiation and indicates, in addition to its function in early gonad development and sex determination, a novel function for Wt1, namely, in Müllerian duct regression.

1999 ◽  
Vol 19 (3) ◽  
pp. 2289-2299 ◽  
Author(s):  
Jungho Kim ◽  
Dirk Prawitt ◽  
Nabeel Bardeesy ◽  
Elena Torban ◽  
Caroline Vicaner ◽  
...  

ABSTRACT Gonadal differentiation is dependent upon a molecular cascade responsible for ovarian or testicular development from the bipotential gonadal ridge. Genetic analysis has implicated a number of gene products essential for this process, which include Sry, WT1, SF-1, and DAX-1. We have sought to better define the role of WT1 in this process by identifying downstream targets of WT1 during normal gonadal development. We have noticed that in the developing murine gonadal ridge, wt1 expression precedes expression of Dax-1, a nuclear receptor gene. We document here that the spatial distribution profiles of both proteins in the developing gonad overlap. We also demonstrate that WT1 can activate the Dax-1 promoter. Footprinting analysis, transient transfections, promoter mutagenesis, and mobility shift assays suggest that WT1 regulates Dax-1via GC-rich binding sites found upstream of the Dax-1 TATA box. We show that two WT1-interacting proteins, the product of a Denys-Drash syndrome allele of wt1 and prostate apoptosis response-4 protein, inhibit WT1-mediated transactivation ofDax-1. In addition, we demonstrate that WT1 can activate the endogenous Dax-1 promoter. Our results indicate that the WT1–DAX-1 pathway is an early event in the process of mammalian sex determination.


Author(s):  
Vladimir Vranic ◽  
Milena Potic Floranovic ◽  
Milan Petrovic ◽  
Srdjan Starcevic ◽  
Gordana Supic

Abstract Osteoarthritis is a degenerative, painful and irreversible disease that affects millions of people worldwide. The causes and mechanisms of osteoarthritis have not been fully understood. Vitamin D is an essential factor in bone metabolism. Its actions are mediated by the vitamin D receptor, a transcription factor that controls gene expression, thus maintaining calcium and phosphate homeostasis. Vitamin D has been hypothesized to play essential role in a number of musculoskeletal diseases including osteoarthritis, and its deficiency is prevalent among osteoarthritis patients. A large number of studies have been done regarding the effects of vitamin D in pathogenesis and progression of osteoarthritis, as well as its use a therapeutic agent. Up to date, studies have provided controversial results, and no consensus concerning this matter was achieved. With this review, we aim to explore current data on the possible role of vitamin D and its receptor in pathogenesis of osteoarthritis and assess the efficiency of vitamin D supplementation as a therapeutic strategy.


Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1329-1341 ◽  
Author(s):  
S. Mundlos ◽  
J. Pelletier ◽  
A. Darveau ◽  
M. Bachmann ◽  
A. Winterpacht ◽  
...  

The human Wilms' tumor gene WT1 encodes a putative transcription factor implicated in tumorigenesis and in specifying normal urogenital development. We have studied the distribution of WT1 protein and mRNA using immunohistochemistry and in situ hybridization. Monoclonal antibodies were raised against a peptide specific to the first alternative splice site of WT1. Two antibodies specifically reacted on Western blot to this WT1 isoform. Immunofluorescence localized WT1 protein to podocytes during mesonephric and metanephric development. In situ hybridization revealed a similar pattern of expression except that WT1 mRNA was also present in metanephric blastema and renal vesicles. Messenger RNA expression was most pronounced in the kidneys during early fetal development and declined thereafter. In contrast, WT1 protein was readily detectable in glomerular podocytes throughout adulthood. WT1 protein in Wilms' tumor was present in blastema and glomeruloid structures. Expression in the female gonad was linked to the different stages of granulosa cell development. In the male gonad, expression was restricted to Sertoli cells and their precursors, the embryonic tunica albuginea and the rete testis. The intracellular distribution of the WT1 protein was investigated by confocal laser microscopy and was demonstrated to be exclusively nuclear. The nuclear distribution and the selective pattern of expression support the proposed role of WT1 as a transcription factor active during urogenital development. The persistence of WT1 expression in the adult kidney suggests a role in homeostasis of the podocyte.


Cell ◽  
1991 ◽  
Vol 67 (2) ◽  
pp. 437-447 ◽  
Author(s):  
Jerry Pelletier ◽  
Wendy Bruening ◽  
Clifford E. Kashtan ◽  
S. Michael Mauer ◽  
J. Carlos Manivel ◽  
...  

JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1005-1009 ◽  
Author(s):  
D. J. Fernbach
Keyword(s):  

2020 ◽  
Vol 3 (11) ◽  
pp. 1100-1104
Author(s):  
Hussein Naeem Aldhaheri ◽  
Ihsan Edan AlSaimary ◽  
Murtadha Mohammed ALMusafer

      The Aim of this study was to determine Immunogenetic expression of  Toll-like receptor gene clusters related to prostatitis, to give acknowledge about Role of TLR in prostatitis immunity in men from Basrah and Maysan provinces. A case–control study included 135 confirmed prostatitis patients And 50 persons as a control group. Data about age, marital status, working, infertility, family history and personal information like (Infection, Allergy, Steroid therapy, Residency, Smoking, Alcohol Drinking, Blood group, Body max index (BMI) and the clinical finding for all patients of Prostatitis were collected. This study shows the effect of PSA level in patients with prostatitis and control group, with P-value <0.0001 therefore the study shows a positive significant between elevated PSA levels and Prostatitis.


Author(s):  
Amanda Denes ◽  
Anuraj Dhillon ◽  
Ambyre L. P. Ponivas ◽  
Kara L. Winkler

Sexual communication is a pivotal part of interpersonal relationships; recent research reveals associations between sexual communication and various relational outcomes. Within the broad domain of sexual communication, current scholarship specifically addresses the role of postsex communication in relationships and its links to physiological and genetic markers. Given these advancements, the present chapter offers an overview of research linking physiology, hormones, and genes to communication after sexual activity. The chapter first presents reviews of two key hormones in sexual communication research: testosterone (T) and oxytocin (O). The oxytocin receptor gene and its link to social behavior broadly, and sexual behavior specifically, is also explored. The chapter then offers a review of several theories relevant to understanding the hormonal underpinnings of sexual communication, as well as future directions for research exploring sexual communication and physiology.


Endocrinology ◽  
2019 ◽  
Vol 161 (2) ◽  
Author(s):  
Sandra Handgraaf ◽  
Rodolphe Dusaulcy ◽  
Florian Visentin ◽  
Jacques Philippe ◽  
Yvan Gosmain

Abstract Characterization of enteroendocrine L cells in diabetes is critical for better understanding of the role of glucagon-like peptide-1 (GLP-1) in physiology and diabetes. We studied L-cell transcriptome changes including microRNA (miRNA) dysregulation in obesity and diabetes. We evaluated the regulation of miRNAs through microarray analyses on sorted enteroendocrine L cells from control and obese glucose-intolerant (I-HFD) and hyperglycemic (H-HFD) mice after 16 weeks of respectively low-fat diet (LFD) or high-fat diet (HFD) feeding. The identified altered miRNAs were studied in vitro using the mouse GLUTag cell line to investigate their regulation and potential biological functions. We identified that let-7e-5p, miR-126a-3p, and miR-125a-5p were differentially regulated in L cells of obese HFD mice compared with control LFD mice. While downregulation of let-7e-5p expression was observed in both I-HFD and H-HFD mice, levels of miR-126a-3p increased and of miR-125a-5p decreased significantly only in I-HFD mice compared with controls. Using miRNA inhibitors and mimics we observed that modulation of let-7e-5p expression affected specifically GLP-1 cellular content and basal release, whereas Gcg gene expression and acute GLP-1 secretion and cell proliferation were not affected. In addition, palmitate treatment resulted in a decrease of let-7e-5p expression along with an increase in GLP-1 content and release, suggesting that palmitate acts on GLP-1 through let-7e-5p. By contrast, modulation of miR-125a-5p and miR-126a-3p in the same conditions did not affect content or secretion of GLP-1. We conclude that decrease of let-7e-5p expression in response to palmitate may constitute a compensatory mechanism contributing to maintaining constant glycemia in obese mice.


Entropy ◽  
2021 ◽  
Vol 23 (6) ◽  
pp. 728
Author(s):  
Zhaofeng Su

Quantum entanglement is not only a fundamental concept in quantum mechanics but also a special resource for many important quantum information processing tasks. An intuitive way to understand quantum entanglement is to analyze its geometric parameters which include local parameters and correlation parameters. The correlation parameters have been extensively studied while the role of local parameters have not been drawn attention. In this paper, we investigate the question how local parameters of a two-qubit system affect quantum entanglement in both quantitative and qualitative perspective. Firstly, we find that the concurrence, a measure of quantum entanglement, of a general two-qubit state is bounded by the norms of local vectors and correlations matrix. Then, we derive a sufficient condition for a two-qubit being separable in perspective of local parameters. Finally, we find that different local parameters could make a state with fixed correlation matrix separable, entangled or even more qualitatively entangled than the one with vanished local parameters.


2019 ◽  
Vol 20 (10) ◽  
pp. 2589 ◽  
Author(s):  
Tatsuya Nagano ◽  
Masahiro Katsurada ◽  
Ryota Dokuni ◽  
Daisuke Hazama ◽  
Tatsunori Kiriu ◽  
...  

Extracellular vesicles (EVs) are circulating vesicles secreted by various cell types. EVs are classified into three groups according to size, structural components, and generation process of vesicles: exosomes, microvesicles, and apoptotic bodies. Recently, EVs have been considered to be crucial for cell-to-cell communications and homeostasis because they contain intracellular proteins and nucleic acids. Epithelial cells from mice suffering from bronchial asthma (BA) secrete more EVs and suppress inflammation-induced EV production. Moreover, microarray analyses of bronchoalveolar lavage fluid have revealed that several microRNAs are useful novel biomarkers of BA. Mesenchymal stromal cell-derived EVs are possible candidates of novel BA therapy. In this review, we highlight the biologic roles of EVs in BA and review novel EV-targeted therapy to help understanding by clinicians and biologists.


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