Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11684 (Uteroglobin)
 114 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uteroglobin, a progesterone-induced uterine protein of the rabbit, is synthesized in cell-free systems as a precursor containing 21 additional amino-acids at its N-terminal end. The mRNA for pre-uteroglobin has been purified from the membrane-bound polysomes of induced endometrium and used as template for the synthesis of a full copy complementary DNA. Final purification of the cDNA was based on hybridization to the template mRNA up to a low value of r0t (0.01 M . s) and digestion of the non-hybridized cDNA by S1 nuclease. A comparison of the hybridization kinetics of the pre-uteroglobin cDNA and rabbit globin cDNA to their respective templates indicates a nucleotide sequence complexity of 650 for pre-uteroglobin mRNA, in agreement with the values obtained by sucrose gradient centrifugation and polyacrylamide gel electrophoresis in formamaide. The melting temperature of the hybrids of pre-uteroglobin cDNA to its template reflects the absence of mismatched sequences. This cDNA has been used to quantify pre-uteroglobin mRNA sequences in the endometrial RNA from control animals and from animals treated sequentially with estradiol and progesterone. In agreement with the induction of uteroglobin-synthesizing activity, there is a dramatic increase in the uterine content of pre-uteroglobin mRNA after hormonal treatment. Part of this effect can be accounted for by hormonally induced cell proliferation. When expressed on a DNA basis there is a 50--100-fold increase in the cellular content of pre-uteroglobin mRNA following hormonal treatment.
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PMID:Synthesis and characterization of a DNA complementary to pre-uteroglobin mRNA. 49 5

Uteroglobin is a protein that is synthesized in large quantities by the rabbit uterine endometrial cells and secreted into the uterine lumen around the time of implantation of the developing blastocysts. The protein is also synthesized constitutively at a low level in the lung. In the uterus, synthesis of the protein is induced by progesterone but repressed by estradiol; whereas in the lung, it is not hormonally responsive. Using a full-length cDNA clone, we have established the nucleotide sequence of uteroglobin mRNA and have determined its levels in uterus and lung during early pregnancy. The clone, pUG617, contains all but 24 nucleotides at the 5' untranslated region of the structural gene. To establish the full mRNA sequence, we isolated a 5' end-labeled DNA fragment from pUG617 and extended its length using reverse transcriptase after hybridization with uterine poly(A)-containing RNA. The 5'-terminal sequence of uteroglobin mRNA was established by sequencing the extended DNA fragment. The nucleotide sequence of the peptide-coding portion of the gene has resolved some previously reported discrepancies in the amino acid sequence of the mature protein and those in the signal peptide. By comparison of sequences with a partial uteroglobin cDNA clone isolated by another laboratory, a polymorphic nucleotide at position 246 of the gene has been identified, where a G-A transition has caused an amino acid substitution from aspartic acid to asparagine at residue 46 of the mature protein. Analysis of steady-state RNA levels in the uterus has shown that the induction and repression of uteroglobin synthesis during early pregnancy is the result of accumulation and depletion of its mRNA, respectively. During the same period in the lung, no consistent changes in uteroglobin mRNA level were evident, reflecting the constitutive levels of the protein in this tissue.
DNA 1981
PMID:Hormonally regulated mammalian gene expression: steady-state level and nucleotide sequence of rabbit uteroglobin mRNA. 629 63

Uteroglobin, a progesterone-binding protein, is expressed in several organs, principally endometrium and lung, of the rabbit and other rodents. The phasic activation of the uteroglobin gene in the endometrium during early pregnancy is regulated by progesterone, which contrasts with the constitutive, nonregulated expression of this gene in the lung. Thus, uteroglobin provides a useful model for the study of differential gene regulation by hormones as well as for the study of steroid-protein interactions.
DNA 1983
PMID:Uteroglobin: a model for the sutyd of progesterone action in mammals. 630 25

A review is given of the comparative pathology of endometrial carcinomas regarding the incidence, the morphology, and the relation with endometrial hyperplasia. Compared to man, endometrial carcinomas in animals are fairly rare, except in rabbits, in cattle, and in a stock of Han: Wistar rats. In rabbits the endometrial carcinomas are mostly primary multiple and present in both horns. Histologically they are almost always adenocarcinomas. The histological structure can vary considerably with regard to the degree of differentiation. In cattle the endometrial carcinomas are mostly singular. Histologically they are mostly adenocarcinomas, often accompanied by formation of much dense fibrous tissue. In rats the endometrial carcinomas are mostly primary multiple adenocarcinomas. In man as well as in the rabbit and in the rat, relationships have been described between endometrial hyperplasia and endometrial carcinoma. It is striking that in the dog, a species in which endometrial hyperplasia very often occurs, endometrial carcinomas should be rare. The endometrial carcinoma in the rabbit as an animal model for human endometrial carcinoma is discussed extensively. In both species there are signs indicating relationships between endometrial carcinomas and sex hormones, especially oestrogens. The incidence in rabbits is very high. Endometrial carcinomas in rabbits can be transplanted subcutaneously in the same rabbit. They can also be cultured in vitro. Moreover the rabbit is a suitable species to study the progesterone/progesterone-receptor complex by determining the synthesis of the progesterone-induced protein uteroglobin which may be important in studying endometrial carcinomas. Uteroglobin is a good marker for a functional 'Progesterone-PR-DNA-mRNAug-Uteroglobin- System' (or PUG-System).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative pathology of endometrial carcinoma. 638 39

Uteroglobin (UG) is a secretory protein produced by the rabbit endometrium and its production is increased during cell differentiation which occurs during early pregnancy or pseudopregnancy. In the present study, the optimal conditions for UG production by rabbit endometrial epithelial cells in culture were examined. Metabolic labeling studies showed the incorporation of [35S]methionine into UG molecules by the endometrial epithelial cells in culture. Accumulation of UG in culture media was linear for at least a period of 24 h. These cells do not catabolize exogenously added radiolabeled UG. Endometrial cells obtained from virgin female rabbits at different times after the administration of human CG (hCG) and put in culture were found to make different amounts of UG. The maximal UG production was found in cells taken from pseudopregnant rabbits 4 days after hCG administration. Cycloheximide (28 micrograms/ml) inhibited the production of UG by the cells in culture whereas actinomycin-D (5 micrograms/ml) and cordycipin (50 micrograms/ml) increased its production. Inhibition of DNA synthesis by hydroxyurea (10(-3) M) did not affect the UG production. The production of UG was significantly less when cells were cultured on attached or floating collagen gels as compared to cells grown on plastic Petri dishes. The amino acid content of Ham's F-12 medium was shown to be adequate for maximal UG production; lowering this amino acid concentration decreased the amount of UG accumulated in the medium over a 24-h period. Increasint the number of cultured cells per dish resulted in an increased UG production per cell.
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PMID:Uteroglobin production by cultured rabbit uterine epithelial cells. 683 58

Uteroglobin has been studied under two aspects: 1) as a model of specific interaction between a protein and a steroid hormone: crystals were obtained and analyzed by X-ray diffraction; 2) as a marker of progesterone action in the endometrium: messenger RNA was translated, purified and transcribed into complementary DNA.
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PMID:[Uteroglobin]. 689 76

Uteroglobin is a predominant protein in the rabbit uterus, where it is induced by progesterone, and occurs also in the lung, where its level is constitutive. A recombinant plasmid containing uteroglobin complementary DNA (cDNA) has been constructed previously from partially purified uteroglobin mRNA. In this study, the cloned uteroglobin cDNA has been used as a probe to determine the cellular content of uteroglobin mRNA at different times in early pregnancy in both rabbit uterus and lung. By RNA-excess hybridization to poly A-enriched RNA and to total nucleic acid extracts an increase in steady-state uteroglobin mRNA level was detected, from approximately 250 molecules/uterine epithelial cell in non-pregnant rabbits to approximately 6800 molecules/cell on day 4 of pregnancy, after which the levels declined progressively up to day 8. The pulmonary level of uteroglobin mRNA was about 400 molecules/cell and did not change significantly with day of pregnancy. The major factor in regulating the production of uteroglobin in the uterus of pregnant rabbits is the accumulation and subsequent depletion of its mRNA.
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PMID:Hybridization analysis of steady-state levels of uteroglobin mRNA in rabbit uterus and lung during early pregnancy. 711 50

Uteroglobin (UG) is a hormonally regulated secretory protein produced in the lung and urogenital system of rabbits. It is homologous to rat and human Clara cell 10 kD protein (CC10); however, there are significant differences in the tissue-specific expression between these species. Mouse CC10 (mCC10) protein has been less well characterized. In this study, we cloned and sequenced the cDNA encoding the mCC10 protein. The mouse cDNA showed 90, 52, and 51% amino acid homology to rat and human CC10 and rabbit UG cDNA, respectively. The cellular and tissue-specific expression of mCC10 was examined in adult and developing mice. Endogenous mCC10 expression was compared with transgenic mice expressing a fusion gene of the rabbit 3.3 kb UG promoter linked to human growth hormone (hGH) as an easily detectable marker. Northern blot analysis detected mCC10 mRNA only in the lung. hGH mRNA was detected in the lung in levels similar to the endogenous mCC10 transcripts. However, it was also present in trace quantities in the uterus and ovary of normal adult female mice and in the epididymus of adult male mice. hGH and mCC10 proteins were identified in the trachea and lung, where they were localized to Clara cells. Ultrastructurally, hGH was present in secretory granules in the Clara cell cytoplasm and appeared to be secreted into the airways. hGH was initially detectable in 16 day gestation developing mice; however, CC10 was not detectable until the eighteenth day of gestation. We have created an attractive model for comparing the cis-acting DNA elements governing the interspecies variation in tissue-specific expression of CC10.
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PMID:Cloning and tissue-specific expression of the cDNA for the mouse Clara cell 10 kD protein: comparison of endogenous expression to rabbit uteroglobin promoter-driven transgene expression. 839 59

The discovery of uteroglobin resulted from investigations on the biochemical composition of oviductal and uterine secretions of the rabbit and other mammals. These determinations about physiological composition were urgently requested to prepare culture media for research on early mammalian development in vitro. Discovery of significant proteins during the sixties reflected the laboratory skills of that time. Protein characterization was achieved by isolation via Sephadex gels, electrophoresis on polyacrylamide gels, and finally immunoprecipitation using classical polyclonal antibodies. The molecular biology was not yet established. Uteroglobin could be found as the major protein component of rabbit uterine secretion. From the beginning, it was already identified as an unusually small, spheric uterine secretory molecule without any carbohydrates--hence its name. Uteroglobin was the first mammalian protein that turned out to be progesterone-regulated and, at the same time, released in mg amounts actually in one organ compartment. Moreover, uteroglobin and its gene proved to be a reliable model for the description of progesterone/progesterone receptor complex action at the DNA level. After its original observation in the uterus, however, uteroglobin was detected also in several other organs, for example, the epididymis, the seminal vesicle, and the lung. Initially, it could not be found in the blood, which challenged the hypothesis that uteroglobin specifically should operate by local activation rather than by a humoral or endocrine effect. Later, though, the human uteroglobin molecule, isolated from blood filtrate, was used for detailed structural analyses. The rabbit uteroglobin model certainly was beneficial for reproductive biological research. Experimental interference with steroid hormone regulation during preimplantation presented surprising effects, which led to the discovery of the transposition of the implantation window. The uterine secretion protein patterns, in particular the uteroglobin fraction and the beta-glycoprotein fraction, served as decisive marker profiles to identify the biological stage of the intrauterine microenvironment during preimplantation. This diagnostic procedure, using only protein parameters, enabled us to precisely predict the receptive stage of the endometrium for donated blastocysts to achieve implantation successfully.
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PMID:The discovery of uteroglobin and its significance for reproductive biology and endocrinology. 1119 82

Uteroglobin (UG) is a multifunctional protein with anti-inflammatory/immunomodulatory properties. The UG gene is located on the long arm of chromosome 11 (11q12.3-q13.1) in a region linked to some immune disorders. A guanine-adenine substitution at position 38 (A38G) has been found in the noncoding region of exon 1 that is significantly correlated with an increased risk of developing immune-mediated diseases. Recently an experimental model of UG knockout mice showed that in mice, UG deficiency causes severe glomerulopathy with mesangial deposition of IgA-fibronectin complexes. To detect the presence of polymorphisms in the UG coding sequence, the DNA of 109 patients with IgA nephropathy (IgAN), and 32 patients with systemic lupus erythematosus (SLE) were tested for the nucleotide sequence of all three UG exons by heteroduplex analysis. We detected heterozygous DNA only for exon 1 due to the A38G substitution, as confirmed by sequencing. We tested for A38G polymorphism, by restriction endonuclease digestion (Sau96I), both in SLE patients and in IgAN patients. Twenty patients with either membranous nephropathy (12) or focal and segmental glomerular sclerosis and 120 healthy subjects served as controls. Compared with both healthy controls and non-IgA control patients, the frequency of the 38A allele was significantly higher in SLE patients (38 of 64 alleles versus 89 of 240 alleles, p = 0.002, and versus 7 of 40 alleles, p < 0.001). IgAN patients showed an allelic distribution similar to both control groups. A subgroup of 18 IgAN patients undergoing renal replacement therapy because of end-stage renal disease showed a significant increase in 38A allele frequency (5 of 36 38G alleles versus 31 of 36 38A alleles, p < 0.001). UG is an immunomodulatory agent that is able to (a) inhibit the activity of several phospholipase A2 (PLA2s), (b) interfere with the function of both neutrophils and monocytes, and (c) prevent immune recognition, perhaps by masking surface antigens. This could account for the role this molecule plays in SLE. The A38G polymorphism is located within a region corresponding to the rat minimal promoter that proved to be important in the transcriptional regulation of UG. Although the significance of any alterations in the UG exon 1 noncoding region in humans has yet to be clarified, initial evidence suggests that it may alter the control of immune response and of inflammation.
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PMID:Polymorphism of the uteroglobin gene in systemic lupus erythematosus and IgA nephropathy. 1200 94


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