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Query: UNIPROT:P11684 (Uteroglobin)
 114 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uteroglobin was obtained from 5 day pregnant rabbits and purified to homogeneity by Sephadex G 75 and DEAE-cellulose chromatographies. Progesterone binding to uteroglobin was decreased by lyophilization and enhanced by SH-reducing agents. Dithiothreitol was more effective than dithioerythritol, and beta-mercaptoethanol was only active at 25 to 100 mM concentrations. SH-blocking agents (iodoacetate, iodoacetamide, phydroxymercuribenzoate and, dithiobisnitrobenzoic acid) inhibited binding. In the absence of SH-reducing agents only one in every 500 uteroglobin molecules bound the hormone, whereas under optimal conditions (20 mM dithiothreitol) one in every two molecules bound progesterone. There was no significant difference in equilibrium dissociation constants under these two conditions. Uteroglobin had a relatively high affinity for progesterone (KD=4.1 X 10(-7)M) but a threefold higher affinity for 5alpha-pregnane-3,20-dione (KD=1.3 X 10(-7)M). Estradiol was bound but non-specifically with a very low affinity, and its binding was not enhanced by SH-reducing agents. Hormonal specificity of binding to uteroglobin was different from that of binding to rabbit uterine progesterone receptor. Various synthetic progestagens (chlormadinone acetate, norethisterone, R5020) were bound to the latter but not to the former protein. Diethylstilbestrol had some affinity (15% of that of progesterone) for uteroglobin and no affinity for the progesterone receptor. Uteroglobin incubated in the presence or absence of cofactors (NADH and NADPH) with or without dithiothreitol did not metabolize progesterone.
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PMID:Interaction of uteroglobin with progesterone, 5alphapregnane-3,20-dione and estrogens. 1 Oct 93

1. The uterine luminal fluid of rabbits treated with estradiol and progesterone contains a protein factor with high affinity for [3-H] progesterone which is not present in the uterine secretion of control rabbits treated with estradiol. 2. This progesterone dependent factor is shown by gel filtration and polyacrylamide gel electrophoresis to be identical with the uterus specific protein uteroglobin, which seems to be required during the preimplantation phase. Uteroglobin specific antiserum, prepared in guinea pigs, completely inhibits the progesterone binding activity of the proteins of the uterine fluid. 3. Progesterone binding to uteroglobin is dependent upon millimolar concentrations of dithioerythritol. At saturation, one molecule of progesterone binds per uteroglobin molecule and the apparent association constant is 2 x 10-6 M-1 at 0 degrees C. 4. The progesterone binding species of uteroglobin exhibits a molecular weight of around 12 000 on polyacrylamide gels containing dodecylsulfate, and of 15 000 upon gel filtration, indicating a non-globular shape. This molecule is compased of two subunits of similar molecular size which are held together by a disulfide bridge among other forces.
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PMID:Binding of progesterone to the proteins of the uterine luminal fluid. Identification of uteroglobin as the binding protein. 16 37

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

Embryo mortality and altered uterine luminal proteins were studied in progesterone-treated rabbits. Progesterone was injected into rabbits on Days -2, -1, and 0 (the day of mating) at doses of .5, 1, and 1 mg, respectively. Normal fertilization rates resulted, however, embryonic death occurred by Day 4. Embryos in progesterone-treated does for up to 3 days survived normally when transferred to normal recipients, whereas Day 4 embryos from treated does exhibited a reduced ability to implant. The uterine fluid (UF) protein pattern was examined on Days 1-7 after mating. Total UF protein levels were significantly greater (p less than .05) in treated animals on Day 4 than in controls. Uteroglobin secretion was significantly advanced (p less than .05) in the treated animals by Day 3. Examination revealed a delay in the time of the arrival of embryos into the uterus in progesterone-treated rabbits. This delay, coupled with the earlier secretion of uteroglobin in the treated- rabbits, suggested a possible asynchrony of approximately 1 day between embryo arrival in the uterus and certain uterine proteins. Embryonic development in vitro and in vivo was examined after exposure to UF collected at various gestational stages. More normal Day 3 morulae placed in UF from Day 3 control and Day 2 progesterone-treated rabbits developed than similar morulae placed in UF from Day 2 controls and Day 3 progesterone-treaded does. Therefore, partial physiologic synchrony was achieved, suggesting that ''asynchronous'' UF can be embryotoxic. It is concluded that the ability of does to produce young at a pregnancy immediately following a progesterone-treated pregnancy was not impaired.
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PMID:Embryo mortality and altered uterine luminal proteins in progesterone-treated rabbits. 55 59

Uteroglobin is a protein secreted by the rabbit uterus in response to progesterone. In cell-free translation systems, the mRNA for uteroglobin codes for a protein larger in size than the secreted protein. To investigate the relationship between these two forms, the NH2-terminal sequences of pre-uteroglobin and of uteroglobin have been determined. Uteroglobin was purified from rabbit uterine flushings and pre-uteroglobin was obtained by immunoprecipitation of the products of translation of poly(A)-rich endometrial RNA in the wheat germ system in the presence of single or multiple radioactive amino acids. Sequencing was performed by automated Edman degradation and the residue at each cycle was identified by chromatography. The larger size of pre-uteroglobin is accounted for by a 21-amino-acid leader sequence, containing 15 hydrophobic residues, at the NH2 terminus. The sequence Thr-Leu-Ala-Leu occurs twice in the leader region. In common with other secretory proteins, the transient hydrophobic extension at the NH2 terminus of pre-uteroglobin may function to assist transfer of the nascent peptide into the lumen of the endoplasmic reticulum, as proposed in the "signal" hypothesis.
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PMID:Progesterone-induced secretory protein. NH2-Terminal sequence of pre-uteroglobin. 76 58

Uteroglobin was measured under various hormonal conditions: pregnancy, pseudopregnancy, pseudopregnancy with exogenous progesterone, pseudopregnancy with exogenous 20alpha-hydroxyprogesterone, ovariectomy with exogenous progesterone, ovariectomy with exogenous estrogen, ovariectomy with exogenous estrogen and progesterone, and ovariectomy with either exogenous progesterone or estrogen and progesterone, plus uterine trauma. In pregnant females, uteroglobin levels diminished sharply after day 9. In pseudopregnancy, high concentrations were maintained through day 14. Although exogenous progesterone did not prevent this decrease in pseudopregnant females, re-elevation occurred in the continued presence of progesterone. A similar pattern of decline and re-elevation was found in ovariectomized females that received injections of estrogen and progesterone. With an increase in estrogen dosage, the period of uteroglobin secretion was shorter and the magnitude lower. Ovariectomized females receiving only progesterone did not manifest a clear uteroglobin diminution. Uterine trauma on day 7 of exogenous steroid administration to ovariectomized females was followed by a diminution in uteroglobin. At the dosage level used, administration of 20alpha-hydroxyprogesterone did not affect the peak uteroglobin secretion occurring on day 5 of pseudopregnancy. Ovariectomized females receiving estrogen or sesame oil vehicle had barely detectable levels of uteroglobin. A uteroglobin-estrogen complex is suggested as a possible inhibitor of uteroglobin synthesis by a feedback inhibition pathway in pseudopregnant females and in ovariectomized females treated with progesterone plus estrogen. In pregnant females, a uteroglobin-estrogen complex and/or the uterine decidual response to implantation could control uteroglobin synthesis.
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PMID:Factors in diminution of uteroglobin secretion in the rabbit. 124 43

The rat Clara cell 17 kDa protein (previously referred to as the rat Clara cell 10 kDa protein) has been reported to inhibit phospholipase A2 and papain, and to also bind progesterone. It has been isolated from rat lung lavage fluid and crystallized in the space group P6(5)22. The structure has been determined to 3.0 A resolution using the molecular replacement method. Uteroglobin, whose amino acid sequence is 55.7% identical, was used as the search model. The structure was then refined using restrained least-squares and simulated annealing methods. The R-factor is 22.5%. The protein is a covalently bound dimer. Two disulfide bonds join the monomers together in an antiparallel manner such that the dimer encloses a large internal hydrophobic cavity. The hydrophobic cavity is large enough to serve as the progesterone binding site, but access to the cavity is limited. Each monomer is composed of four alpha-helices. The main-chain structure of the Clara cell protein closely resembles that of uteroglobin, but the nature of many of the exposed side-chains differ. This is true, particularly in a hypervariable region between residues 23 and 36, and in the H1H4 pocket.
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PMID:Refined structure of rat Clara cell 17 kDa protein at 3.0 A resolution. 156 Apr 60

The purpose of this study was to investigate the localization and transport of uteroglobin in normal rabbit blastocysts (day 4-day 6 p.c.) and in those cultured for 6-48 h in vitro, using a specific radioimmunoassay and immunocytochemistry. The results of the radioimmunoassay showed that in day 4 p.c. blastocyst tissue (based on homogenate measurements) a significant decrease of the uteroglobin content started after only 6 h of culture in vitro. A significant concomitant rise of uteroglobin was observed in the culture medium after 12 h of in vitro culture. Using immunocytochemistry it was not possible to detect uteroglobin in any compartment of the non-cultured or in vitro cultured day 4 p.c. blastocysts. The efflux of uteroglobin down a concentration gradient was confirmed by the immunocytochemistry in non-cultured and in vitro cultured day 5 p.c. and day 6 p.c. blastocysts. Uteroglobin immunoreactions were mainly detected in non-cultured blastocysts (day 5 and 6 p.c.) in large vesicles of the trophoblast cells. In addition endocytotic vesicles at the inside of the apical membrane of trophoblast cells, some cell debris within the perivitelline space and the neozona were labelled. During in vitro culture of day 5 and 6 p.c. blastocysts, uteroglobin labelling in the coverings did not change. In non-cultured and cultured day 5 and 6 p.c. blastocysts neither the compartments of the embryoblast, the endoderm cells nor the blastocyst cavity showed any uteroglobin immunoreactions. After only 6 h of in vitro culture, uteroglobin immunoreactions were no longer found within the trophoblast cells. The reaction did not reappear during the course of in vitro culture up to 48 h, suggesting a complete lack of de novo synthesis of uteroglobin by blastocysts.
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PMID:Effect of in vitro culture on the dynamics of uteroglobin distribution in rabbit blastocysts. 203 47

To understand the molecular mechanism of endometrial differentiation we have initiated an analysis of the uteroglobin promoter. Uteroglobin is normally expressed in endometrial tissues under the control of ovarian hormones. In gene transfer experiments with the Ishikawa cell line, derived from a human endometrial adenocarcinoma, we have identified several regions in the promoter of the uteroglobin gene that are responsible for its endometrium-specific expression. To evaluate the generality of these findings, we have begun cloning the promoter regions of potential endometrial markers, including the rat, mouse, and human uteroglobin gene. In the rat, expression of the uteroglobin-like gene, CC10, is dominant in the lung but is also observed in the endometrium of progesterone treated animals. A comparison of the 5'-flanking sequence of the rat and rabbit uteroglobin gene resulted in the detection of similarities and differences that could explain their differential expression in vivo. To substantiate these findings we have established several cell lines from rat endometrium using murine retroviral vectors containing a positive selection marker and various viral oncogenes, such as SV40 large T antigen, adenovirus E1A, and Ha-ras. Cell lines immortalized by SV40 T-antigen were subsequently transformed with the Ha-ras oncogene. Several cell lines exhibit properties of epithelial endometrial cells. Two cell lines generated with a temperature sensitive mutant of the SV40 large T-antigen grow as transformed cells at the permissive temperature, but differentiate upon shifting to the non-permissive temperature. These rat endometrial cell lines should be useful for the analysis of endometrium-specific gene expression and as model systems for endometrial carcinoma.
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PMID:Expression of the uteroglobin promoter in epithelial cell lines from endometrium. 206 10

Uteroglobin is expressed in various tissues of the rabbit under complex hormonal control. In the endometrium the uteroglobin gene is transcribed only in epithelial cells after administration of ovarian hormones. In this paper we demonstrate that within the promoter region of the rabbit uteroglobin gene, there is a functional estrogen-responsive element (ERE) located between -265 and -252. Hybrid constructions containing sequences of the uteroglobin promoter up to -299, linked to the chloramphenicol acetyltransferase gene of E. coli respond to estrogens in gene transfer experiments, whereas a deletion that removes half of the ERE does not. A synthetic oligonucleotide corresponding to the putative ERE is able to confer estrogen inducibility to an otherwise unresponsive promoter. Binding experiments with purified estrogen receptor from calf uterus reveal a DNase-I footprint over the ERE. Within this protected region six guanine residues that have been shown to be contacted by the receptor in other EREs are protected against methylation by dimethylsulfate in the presence of the estrogen receptor. We compare this ERE with the vitellogenin A2 ERE from Xenopus and find that the relative affinity of the uteroglobin ERE is slightly lower than that of the vitellogenin ERE. Thus, this uteroglobin ERE could be involved in physiological regulation of uteroglobin expression in the genital tract.
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PMID:The uteroglobin promoter contains a noncanonical estrogen responsive element. 228 Jul 77


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