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Query: UNIPROT:P06889 (Mol)
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Using two oligoprimers derived from the bovine placental estrogen sulfotransferase sequence, we amplified a probe for human placental estrogen sulfotransferase. Using this probe to screen a human placental cDNA library constructed in lambda gt11, we isolated a cDNA clone of 1.3 kb encoding human estrogen sulfotransferase. DNA analysis predicts a protein of 295 amino acids with a calculated molecular weight of 34,199. Alignment of the amino acid sequence with other sulfotransferases indicates that human placental estrogen sulfotransferase shares 68.6, 68.2 and 65.9% similarity with bovine placental, guinea pig adrenocortical, and rat liver estrogen sulfotransferase, respectively. It shows also 95.6, 57.6, 85.3, and 54.2% similarity to human phenol, human DHEA, rat phenol, and rat hydroxysteroid sulfotransferase, respectively. Transfection of expression vectors encoding human estrogen sulfotransferase and dehydroepiandrosterone (DHEA) sulfotransferase in human adrenal adenocarcinoma SW-13 cells indicates that estrogen sulfotransferase transforms estrone more specifically, whereas DHEA sulfotransferase is more specific for DHEA and pregnenolone.
Mol Cell Endocrinol 1994 Feb
PMID:Cloning and expression of cDNA encoding human placental estrogen sulfotransferase. 818 49

MCF-7 human mammary carcinoma cells have been reported to possess beta-estradiol and dehydroepiandrosterone sulfotransferase activities. These steroid sulfotransferase activities may be important in the metabolism and activity of different steroids in these cells. This report describes and characterizes both the enzymatic activity of three cytosolic sulfotransferases found in MCF-7 cells and the corresponding immunoblot analysis of these enzymes with specific anti-sulfotransferase antibodies. Two cytosolic sulfotransferases have been purified and characterized from human tissues which are capable of sulfating estrogens. These are the phenol-sulfating form of phenol sulfotransferase (P-PST) and the hydroxysteroid sulfotransferase, dehydroepiandrosterone sulfotransferase (DHEA-ST). The results of this study show that P-PST is the major cytosolic sulfotransferase found in MCF-7 cytosol and is responsible for most of the beta-estradiol sulfation in these cells. Although DHEA-ST activity was found in MCF-7 cytosol, this activity was only about 3% of the P-PST activity. Immunoblot analysis of MCF-7 cytosol detected both P-PST and lower levels of the monoamine-sulfating form of PST; however DHEA-ST could not be detected apparently because of low levels of expression. Human liver P-PST was expressed in Cos-7 Green monkey kidney fibroblasts and the ability of the cloned enzyme to sulfate beta-estradiol was investigated. This study indicates that P-PST is the prevalent cytosolic sulfotransferase in MCF-7 cytosol and is responsible for the majority of beta-estradiol sulfation in these cells.
J Steroid Biochem Mol Biol 1993 Oct
PMID:Identification and characterization of cytosolic sulfotransferase activities in MCF-7 human breast carcinoma cells. 821 78

The enzymatic synthesis of [3H]5-pregnen-3 beta-ol-20-one sulfate using [3H]5-pregnen-3 beta-ol-20-one, 3'-phosphoadenosine-5'-phosphosulfate and hydroxysteroid sulfotransferase 1 purified from rat liver is reported. The described procedure allowed the obtainment of high specific activity [3H]5-pregnen-3 beta-ol-20-one sulfate in yields ranging from 78 to 86% with respect to [3H]5-pregnen-3 beta-ol-20-one. Two-dimensional thin-layer chromatography was used to purify [3H]5-pregnen-3 beta-ol-20-one sulfate which upon solvolysis resulted in the formation of [3H]5-pregnen-3 beta-ol-20-one. The identity both of the synthesized compound and the solvolysed one was confirmed by reversed-phase high pressure liquid chromatography, and 2-dimensional thin-layer chromatography.
J Steroid Biochem Mol Biol 1993 Nov
PMID:Enzyme-catalyzed synthesis of radiolabeled 5-pregnen-3 beta-ol-20-one sulfate. 824 Sep 86

Between about 50 and 58 days of gestation, the guinea pig chorion becomes attached in its entirety to the uterine wall, suggesting a facilitation of transfer of agents such as steroids between these tissues. At a time between 59 and 64 days, relaxation of the pubic symphysis starts, and anywhere from 5 to 8 days after that event delivery takes place. The present in vitro study was undertaken to evaluate estrone sulfate as a substrate for local production of estradiol, via the action of estrogen sulfatase and 17-hydroxysteroid dehydrogenase, in chorion, endometrium and myometrium taken at four distinct stages of gestation, as follows: 50 days, representing pre-chorion attachment to the uterus (stage 50); 1 or 2 days before pubic symphysis relaxation (minus 1 day, or -1 day); 1 day following relaxation (+1 day); and 1-2 days before delivery (late, or L). At these same stages, the metabolite patterns formed from estradiol were evaluated for endometrium and myometrium. Each of the tissues behaved somewhat differently. Overall hydrolysis of estrone sulfate by endometrium and myometrium exceeded that by chorion. Generation of free steroid from estrone sulfate increased 3-fold in chorion between stages 50 and -1 and during this period estradiol production from estrone sulfate increased 9-fold and continued to rise until delivery. Cytosolic estrogen sulfotransferase activity of chorion decreased 7-fold between stages 50 and -1. This suggested a tissue environment geared to producing potentially active estradiol. However, myometrium converted very little estrone into estradiol until just before delivery despite the facile formation of estrone from estradiol at stages -1, +1 and L. The control of estrogen metabolism by interaction of tissues in the uterus and by some form of enzyme regulation in these tissues suggests a possible role for locally produced estrogen in the stages leading up to parturition.
J Steroid Biochem Mol Biol 1993 Mar
PMID:Generation of estradiol within the pregnant guinea pig uterine compartment with special reference to the myometrium. 846 Dec 61

During the secretory phase of the human menstrual cycle, the endometrium is minimally responsive to the estrogens secreted from the ovaries. Conjugation of beta-estradiol (E2) with sulfate is thought to be an important mechanism in the regulation of the levels of active E2 in endometrial tissue. Estrogen sulfation is reportedly increased during the secretory phase in response to the high levels of progesterone secreted by the ovaries. Estrogen sulfotransferase (hEST), a distinct form of human cytosolic sulfotransferase (ST) with an affinity for E2 and estrone at low nanomolar concentrations, has recently been cloned and expressed in mammalian cells and in bacteria (J Steroid Biochem Mol Biol 52:529, 1995). At least two other forms of human cytosolic ST, dehydroepiandrosterone ST (hDHEA-ST) and the phenol-sulfating form of phenol-ST (hP-PST), also conjugate estrogens but at micromolar concentrations. This report describes the specific induction of hEST in human Ishikawa endometrial adenocarcinoma cells by progesterone as a model for the increases in estrogen sulfation observed in women during the secretory phase of the menstrual cycle. Treatment of Ishikawa cells with 10 microns progesterone for 48 h resulted in a 7-fold increase in the sulfation of 20 nM E2. The sulfation of selective substrates for human dehydroepiandrosterone sulfotransferase (hDHEA-ST) and the two forms of phenol sulfotransferase (hP-PST, hM-PST) were not affected by treatment with progesterone. The levels of immunoreactive hEST and hEST mRNA in the Ishikawa cells were both increased by progesterone, whereas the levels of immunoreactive hDHEA-ST, hP-PST, and hM-PST were not altered. hEST activity was not induced by treatment of Ishikawa cells with varying concentrations of E2, testosterone, or cortisol. The induction of hEST by progesterone was inhibited by RU-486, indicating that progesterone is acting via the progesterone receptor. These results indicate that progesterone is capable of specifically inducing hEST and estrogen sulfation in human Ishikawa adenocarcinoma cells and suggest a mechanism for increasing estrogen sulfation in the endometrium during the secretory phase of the menstrual cycle.
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PMID:Regulation of estrogen sulfotransferase in human endometrial adenocarcinoma cells by progesterone. 862 16

The activities of estrogen sulfotransferase, estrogen sulfatase and estradiol 17beta-dehydrogenase change considerably in the guinea pig uterine compartment during gestation. This study was undertaken to inquire if the chorion membrane could influence the pattern of estrogen resulting when substrates were applied to the fetal surface of the chorion while it was attached, late in gestation, to the uterine wall. This tissue system resulted in a differential handling of estrone and estradiol. Estrone was largely excluded from the tissue, remaining mainly in free steroidal form. Estradiol was considerably converted to its 3-sulfate which was mainly retained by the chorion. Parallel experiments with chorion and uterus separately failed to discriminate between the two substrates. Hydrolysis of estrone sulfate and estradiol 3-sulfate was similar in all three tissue systems. It appears that the interaction of chorion with uterus late in gestation causes a difference in tissue action towards the two steroid substrates of closely related structure. The results suggest a limitation in tissue uptake of estrone compared with estradiol, or a much greater sulfotransferase activity towards estradiol. Whole cytosols of late gestational chorion catalyzed sulfation of estradiol at about double the velocity of estrone. This may only partly account for the difference in the intact chorion-uterine tissue system.
J Steroid Biochem Mol Biol 1996 Dec
PMID:Sulfation by guinea pig chorion and uterus: differential action towards estrone and estradiol. 901 Mar 53

Dietary intake of the essential trace element selenium (Se) regulates expression of genes for selenoproteins and certain non-Se-containing proteins. However, these proteins do not account for all of Se's biological effects. The objective of this work was to identify additional genes whose expression is regulated by Se. Identification of these genes may reveal new functions for Se or define mechanisms for its biological effects. Weanling male Sprague-Dawley rats were fed a Torula yeast-based Se-deficient basal diet or the same diet supplemented with 0.5 mg Se/kg diet as sodium selenite for 13 weeks. Total RNA was used as template for RNA fingerprinting. Two differentially expressed cDNA fragments were identified and cloned. The first had 99% nucleotide identity with rat liver estrogen sulfotransferase (EST) isoform-6. The second had 99% nucleotide sequence identity with rat liver alpha 2u-globulin. The mRNA levels for both were markedly reduced in Se deficiency. Laser densitometry showed that EST mRNA in Se deficiency was 7.3% of that in Se-adequate rat liver. The level of alpha 2u-globulin mRNA in Se-deficient rat liver was only 12.6% of that in Se-adequate rat liver. These results indicate that dietary Se may play a role in steroid hormone metabolism in rat liver.
J Steroid Biochem Mol Biol 1998 Mar
PMID:Selenium regulates gene expression for estrogen sulfotransferase and alpha 2U-globulin in rat liver. 961 24

Using reverse transcriptase-polymerase chain reaction amplification it was possible to detect the presence of type 1 human estrogen sulfotransferase (hEST1) mRNA in the hormone-dependent: MCF-7 and T-47D, and hormone-independent: MDA-MB-231 and MDA-MB-468, human breast cancer cells. The expression of this mRNA is significantly higher in the MDA-MB-468 cells and a correlation of this mRNA expression with the enzymatic activity was observed. The progestin promegestone (R-5020) at a low concentration (5 x 10(-7) M) can significantly increase the estrogen sulfotransferase activity and its mRNA in the hormone-dependent MCF-7 and T-47D cells. As estrogen sulfates are biologically inactive, the stimulatory effect on sulfotransferase by promegestone may open attractive possibilities in the control of estradiol in human breast cancer.
J Steroid Biochem Mol Biol 1998 Sep
PMID:Human estrogen sulfotransferase (hEST1) activities and its mRNA in various breast cancer cell lines. Effect of the progestin, promegestone (R-5020). 974 35

Silencing is a universal form of transcriptional regulation in which regions of the genome are reversibly inactivated by changes in chromatin structure. Sir2 (Silent Information Regulator) protein is unique among the silencing factors in Saccharomyces cerevisiae because it silences the rDNA as well as the silent mating-type loci and telomeres. Discovery of a gene family of Homologues of Sir Two (HSTs) in organisms from bacteria to humans suggests that SIR2's silencing mechanism might be conserved. The Sir2 and Hst proteins share a core domain, which includes two diagnostic sequence motifs of unknown function as well as four cysteines of a putative zinc finger. We demonstrate by mutational analyses that the conserved core and each of its motifs are essential for Sir2p silencing. Chimeras between Sir2p and a human Sir2 homologue (hSir2Ap) indicate that this human protein's core can substitute for that of Sir2p, implicating the core as a silencing domain. Immunofluorescence studies reveal partially disrupted localization, accounting for the yeast-human chimeras' ability to function at only a subset of Sir2p's target loci. Together, these results support a model for the involvement of distinct Sir2p-containing complexes in HM/telomeric and rDNA silencing and that HST family members, including the widely expressed hSir2A, may perform evolutionarily conserved functions.
Mol Biol Cell 1999 Sep
PMID:The conserved core of a human SIR2 homologue functions in yeast silencing. 1047 45

Although silencing is a significant form of transcriptional regulation, the functional and mechanistic limits of its conservation have not yet been established. We have identified the Schizosaccharomyces pombe hst4(+) gene as a member of the SIR2/HST silencing gene family that is defined in organisms ranging from bacteria to humans. hst4Delta mutants grow more slowly than wild-type cells and have abnormal morphology and fragmented DNA. Mutant strains show decreased silencing of reporter genes at both telomeres and centromeres. hst4(+) appears to be important for centromere function as well because mutants have elevated chromosome-loss rates and are sensitive to a microtubule-destabilizing drug. Consistent with a role in chromatin structure, Hst4p localizes to the nucleus and appears concentrated in the nucleolus. hst4Delta mutant phenotypes, including growth and silencing phenotypes, are similar to those of the Saccharomyces cerevisiae HSTs, and at a molecular level, hst4(+) is most similar to HST4. Furthermore, hst4(+) is a functional homologue of S. cerevisiae HST3 and HST4 in that overexpression of hst4(+) rescues the temperature-sensitivity and telomeric silencing defects of an hst3Delta hst4Delta double mutant. These results together demonstrate that a SIR-like silencing mechanism is conserved in the distantly related yeasts and is likely to be found in other organisms from prokaryotes to mammals.
Mol Biol Cell 1999 Oct
PMID:The Schizosaccharomyces pombe hst4(+) gene is a SIR2 homologue with silencing and centromeric functions. 1051 58


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