Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.6.1 (sulfatase)
3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Placental sulfatase deficiency has been found in four pregnancies (cases 1 to 4) with inappropriately low levels of urinary estriol excretion (less than 1.3 mg. per day near term gestation) associated with healthy neonates. The basis of the diagnosis in these cases was the greatly limited capacities for hydrolysis of 14C-dehydroepiandrosterone sulfate (DHA-S) and 3H-estrone sulfate (0.2 mugCi each) to the free steroids during incubation of placental homogenates. Placental aromatase activities in vitro for free DHA and the concentrations of appropriate estrogen precursors in cord blood were normal or elevated. The defect was diagnosed prenatally in two of these cases on the basis of failure to increase the maternal excretion of urinary estriol (0.6 to 0.7 and 1.3 to 1.3 mg. per day, respectively) following acute instillation of DHA-S (250 mg.) into the amniotic fluid and on normal levels of estrogen precursors in cord blood. In comparison, a twofold increase in maternal estriol excretion was observed after infusing DHA-S into the amniotic cavity of a "high-risk" pregnancy having normal sulfatase and aromatase activities in vitro (case 5). These enzyme activities were also found to be similarly normal in another placenta from an undergrown fetus (case 6) and in six normal placentas. The clinical features of these pregnancies, the first ones described from the western hemisphere, are similar to reported cases: the newborn progeny are healthy males who appear to be developing normally. The prenatal diagnosis of the sex-specific placental enzyme defect has been made possible by the use of an intra-amniotic DHA-S loading test.
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PMID:Diagnosis of placental sulfatase deficiency.. 13 74

Of the total number of breast cancers approx. 30-50% are hormone-dependent and estradiol is one of the main factors of cancerization. Consequently, the control of this hormone inside the cancer cell is of capital importance because it is well established that the inhibition of estradiol biosynthesis can have a positive effect on the evolution of the disease. The blockage of estradiol can be obtained by the action of anti-aromatases, anti-sulfatases, the control of the 17 beta-hydroxysteroid dehydrogenase activity or by the stimulation of the sulfotransferase which converted the estrogens in their sulfates. In breast cancer tissue estrone sulfate is quantitatively the most important source of estradiol. In the intact cell, estrone sulfatase activity is very intense in the hormone-dependent cell lines (e.g. MCF-7, T-47D) but very small activity is observed in the hormone-independent (e.g. MDA-MB-231, MDA-MB-436) cell lines. However, this activity became very strong after homogenization in the hormone-independent cells, suggesting the presence of repressive factor(s) for this enzyme or its sequestering in an inactive form, in the intact cells of these cell lines. In a series of previous studies it was found that in hormone-dependent cell lines different anti-estrogens: tamoxifen and derivatives, ICI 164,384, very significantly decrease the estradiol concentration originated from estrone sulfate, and recently it was observed that Decapeptyl (D-Trp6-gonadotropin-releasing hormone) in the presence of heparin can also decrease the conversion of estrone sulfate into estradiol. No significant effect was obtained in the presence of heparin or Decapeptyl alone. The estrone sulfatase activity can be inhibited by progesterone, the progestagen R-5020, and testosterone. In another series of recent studies the presence of very strong estrogen sulfotransferase activity has been shown in one breast cancer cell line, the MDA-MB-468. We can conclude that: (1) the control of estradiol concentration can be carried out in the breast cancer tissue itself; (2) estrone sulfate can play an important role in the bioavailability of estradiol in the breast cancer cell; and (3) as is the case for the aromatase, the control of: the estrogen sulfatase, estrogen sulfotransferase, and 17 beta-hydroxysteroid dehydrogenase can be new targets for therapeutic applications in breast cancer.
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PMID:Recent data on estrogen sulfatases and sulfotransferases activities in human breast cancer. 158 Sep 21

A description is presented of the first documented case of placental aromatase deficiency. The deficiency caused maternal virilization during pregnancy and pseudohermaphroditism of the female fetus. A 24-yr-old primigravida showed progressive virilization during the third trimester. Urinary excretion of estrogen was less than 14 mumol/day between 35-38 weeks of pregnancy, although nonstress tests showed reactive patterns and serum levels of human placental lactogen were above 460 nmol/L. Maternal serum levels of estrogens were low, and those of androgens were high in the third trimester. A dehydroepiandrosterone sulfate loading test induced a marked increase in maternal serum levels of androgens, whereas no such increase was observed in estrogens. The woman delivered vaginally a live full-term infant who exhibited female pseudohermaphroditism. Cord serum levels of estrogens were extremely low, while those of androgens were high. The aromatase activity of the placenta, determined by the conversion of [7-3H]androstenedione to 17 beta-[7-3H]estradiol and [7-3H]estrone, were less than 0.03 fmol/microgram protein.min (control, 9.6 +/- 2.2 fmol/microgram protein.min). The sulfatase activity of the placenta was 0.63 pmol/microgram protein.min compared to 0.46 +/- 0.16 pmol/microgram protein.min in controls. The rate of aromatization by normal control placentas was the same as that obtained during coincubation of samples of normal placentas and that of the patient. Thus, the presence of aromatase inhibitor in the patient's placenta was excluded.
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PMID:A new cause of female pseudohermaphroditism: placental aromatase deficiency. 182 97

We have compared hormone production by early gestation and term human placental trophoblasts cultured in Ham's F10 medium containing 10% fetal bovine serum with that by cells cultured in serum-free HB102 medium. Mean daily production of progesterone on Days 3 to 7 was approximately 25% less by both early gestation and term cells cultured in HB102 as compared to Ham's F10, but production was maintained at a stable level for at least 7 d longer than the cells in Ham's. Estradiol production from 10(-6) M dehydroepiandrosterone by both early gestation and term cells was comparable in both media. Human placental lactogen production on Days 3 to 7 was 40% less by cells cultured in HB102. Human chorionic gonadotropin (hCG) output by early gestation cells was also 50% less in HB102 but term cells in HB102 produced twice as much hCG as those in Ham's F10. 3B-Hydroxysteroid dehydrogenase (3BHSD) activity in early gestation and term cells and 11B-hydroxysteroid dehydrogenase (11BHSD) activity of early gestation cultures was comparable in the two media. 11BHSD activity was decreased in the term cultures, and this decrease was more marked in Ham's than in HB102. Sulfatase and aromatase activities in the early gestation cultures were comparable in both media; sulfatase activity was comparable and aromatase activity only 20% less in the term cells cultured in HB102. These results indicate that serum-free HB102 supports differentiated function of human trophoblast cells and is useful for studies of placental activity for as long as 14 d in culture.
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PMID:A serum-free system for culturing human placental trophoblasts. 222 3

The well-known hormone dependency of the normal human prostate and of BPH and prostatic carcinoma stimulated the study of cellular events which would possibly lead to specific steroid hormone patterns under the respective prevailing condition. In extending earlier observations on a significant DHT and E2 accumulation especially in stromal nuclei of BPH recent data on the uptake and metabolism of adrenal androgens clearly underline the important differential role of either stromal or epithelial cells. Epithelium and stroma of BPH contained a quantitatively different pattern of steroid metabolizing enzymes. This dualism of enzyme activity favours the conversion of testosterone to DHT in the stroma while androgens of adrenal origin are metabolized mainly in BPH epithelium. Further to quantitative data on the intracellular distribution of the three sex steroid classes (estrogens, androgens, adrenal androgens) and to Km and Vmax values of the respective steroid metabolizing enzymes in question (5 alpha-reductase, 3 alpha/beta-HSDH, 17 beta-HSDH, sulfatase, aromatase) the impact of antihormones (cyproterone acetate) on the intratissular distribution and on the in vivo cytosolic and nuclear binding of DHT as well as on its biological implications will be discussed. The data present a complicated picture, which points to special roles of epithelial and stromal cells and allow speculations on the relative importance of testicular and adrenal androgens and estrogens for the development and maintenance of both normal and diseased human prostates. Furthermore, the determination of intratissular steroid concentrations can be an important tool to understand and to ground a rational basis for a hormonal treatment of prostatic tumors.
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PMID:Intratissular androgens in benign prostatic hyperplasia and prostatic cancer. 243 5

The activities of aromatase and estrone sulfatase which are important enzymes involved in the local production of estrogen in breast cancer tissue were measured to examine their availability in endocrine therapy and their clinical significance. The materials obtained were breast cancer tissue, noncancerous mammary gland and breast fat tissue from twenty eight patients with breast cancer, and mammary gland tissue from eight patients with benign breast disease. After centrifugation of homogenized tissue at 1000 X g, the supernatant of breast cancer tissue or mammary gland and the subnatant of breast fat tissue were used as enzyme sources. Aromatase activity was measured by 3H2O release assay using (1 beta-3H) androstenedione as the substrate, while estrone sulfatase activity was estimated from the conversion rate of (6,7-3H)estrone-3-sulfate to estrone. Aromatase activities were 25.1 +/- 12.4 (mean +/- S.D.) fmol/mg protein/h in twenty seven breast cancer tissue specimens, 11.0 +/- 6.1 fmol/mg protein/h in sixteen noncancerous mammary gland tissue specimens, 9.3 +/- 10.0 fmol/mg protein/h in twenty seven breast fat tissue specimens, and 7.7 +/- 5.5 fmol/mg protein/h in eight mammary gland tissue specimens from patients with benign breast disease. The aromatase activity in breast cancer tissue was significantly higher than that in noncancerous mammary gland, breast fat tissue and benign breast lesions (p less than 0.001). Estrone sulfatase activity was 4.0 +/- 3.5 nmol/mg protein/h in nineteen breast cancer tissue specimens, but was almost undetectable in eleven noncancerous mammary tissue specimens and eight benign breast lesions. These results suggest the relatively high local production of estrogen, mediated by aromatase or estrone sulfatase in breast cancer tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Local production of estrogen via aromatase and estrone sulfatase in breast cancer tissue]. 279 62

Dehydroepiandrosterone sulfate (DHEAS) determination in biological fluids was carried out by enzymatic hydrolysis and conversion into estrogens [estrone (E1) and estradiol (E2)] by the multienzyme system of human placental microsomes. The enzymatic complex consists of sulfatase, 3 beta-hydroxysteroid oxido reductase and 5en----4en isomerase which converts DHEAS into androstenedione (A); the latter component is further converted into estrogens by the aromatase. The resulting estrogens were determined from the NADH formed by the transhydrogenation reactions of human placental dehydrogenase. NADH was measured by bioluminescence. As little as 4 pg was assayable by this rapid enzymatic method, with a coefficient of variation of 8%. The results are in good agreement with radioimmunoassay and the method is suitable for routine use.
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PMID:Bioluminescence: an improvement in the enzymatic assay of dehydroepiandrosterone sulfate in biological fluids. 295 62

To study the mechanism of production of estrogen during pregnancy, the following in vitro and in vivo studies were undertaken; 1) Weight of human placenta and total estradiol (E2) levels in the maternal peripheral vein were measured at different weeks of gestation. 2) Changes in E2 levels after DHA-S 100mg loading were calculated at the 1st, 2nd and 3rd trimesters. 3) Steroid enzyme activities including sulfatase, 3 beta-HSD and aromatase in placenta obtained in the 1st, 2nd and 3rd trimesters were measured. Results were as follows; 1) The weight of the human placenta increased gradually as gestation progressed. Twofold placental weight was noticed from the 2nd to the 3rd trimester. 2) Total E2 in the maternal peripheral vein increased steadily, being 4.07 +/- 1.74 ng/ml at the 1st trimester, 27.72 +/- 11.67 ng/ml and 104.12 +/- 57.89 ng/ml at the 2nd and 3rd trimesters respectively. The increase in E2 from the 2nd to the 3rd trimester was greater than that of the placental weight. 3) Increases in E2 following DHA-S loading were 1.01 ng/ml at the 1st, 29.2 ng/ml at the 2nd and 98.2 ng/ml at the 3rd trimester. 4) No significant differences were observed between placental 3 beta-HSD and sulfatase activities in the placenta obtained at the three different stages of pregnancy, while aromatase activity was found to be significantly higher in the placenta of the 3rd trimester than that of 2nd trimester. These results indicate that the remarkable increase in estrogen production in the 3rd trimester may be explained partially by increased aromatizing enzyme activity in the placenta.
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PMID:[Changes in placental enzymatic activities in relation to estrogen production during pregnancy]. 315 58

Aromatase has been identified in the telostean, avian, and mammalian pituitaries, although its cellular location(s) is not yet certain. To address this question, experiments were performed in tilapia (Oreochromis mossambicus), a species which has been well characterized with respect to the intraglandular distribution of the different pituitary cell types. To estimate aromatase, glands were microdissected into rostral pars distalis (RPD), proximal pars distalis (PPD), and neurointermediate lobe (NIL) and organs were cultured in the presence of [3H]androstenedione for 16-24 hr. [3H]Estrogen products were isolated and quantified after ether extraction, hydrolysis with glucuronidase-sulfatase, thin-layer chromatography, and phenolic partition. Authentic estrone or estradiol-17 beta were produced by all pituitary regions and also by the urophyseal region of the spinal cord. Aromatase was two to five times higher in PPD than in RPD or NIL and similar to activity in adjacent hypothalamus-preoptic area (HPOA). Much lower estrogen yields were obtained in cultures of cerebellum, urophysis, and other cord regions. Since the PPD contains most of the somatotropes, these data are consistent with earlier studies implicating GH3/GH4 cell strains as an enriched enzyme source, although its presence in other cell types cannot be ruled out. The unusually high and localized aromatase in tilapia pituitary renders this species a useful model for studying the targets and functional importance of estrogen as a parahormone in the pituitary.
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PMID:Aromatase is concentrated in the proximal pars distalis of tilapia pituitary. 341 Feb 99

One-third of the cases of breast cancer in postmenopausal women are hormone-dependent and the lesions regress upon treatment with antiestrogens or inhibition of estrogen biosynthesis. In these patients, estrogens are synthesized in extraglandular tissues from adrenal precursors and re-enter plasma to produce estrone levels of 52 +/- 6.5 pg/ml (mean +/- SEM) and estradiol concentrations of 13.1 +/- 0.7 pg/ml. However, the fact that the levels of estrogen in breast tumor tissue are an order of magnitude higher than plasma levels suggested the possibility of in situ estrogen production. To address this possibility, we measured several enzymes involved in estradiol biosynthesis in human tumors. Forty-eight of 61 tumors contained aromatase (estrogen synthetase) activity ranging from 5-80 pg/gm protein per hour. By comparison, the levels of estrone sulfatase were 10(6) higher, ranging from 0.8-125 micrograms/gm protein per hour. Because the sulfatase enzyme was of lower affinity (i.e., Km = 27 microM) than that of aromatase (i.e., 0.027 microM), the amount of estrogen formed under conditions of similar substrate concentrations was compared and found to be 10-fold higher via the sulfatase enzyme. In 41 additional tumors, the 17 beta-hydroxysteroid dehydrogenase enzyme, catalyzing the conversion of estrone to estradiol, was uniformly present. To test the biologic relevance of the estrone sulfate to estrone to estradiol pathway, estrogen-dependent nitrosomethylurea rat mammary tumors were grown in soft agar in the presence of estrone sulfate. Concentrations of estrone sulfate of 10(-6) microM significantly (p less than 0.01) stimulated colony formation in this system in which 75.5-98.6% of estrone sulfate was converted to estrone and 0.2 to 6% to estradiol. These data support the hypothesis that mammary carcinomas can synthesize estradiol in situ from circulating estrogen precursor and that local conversion is biologically important. On the basis of comparative data, the estrone sulfate to estrone to estradiol pathway is quantitatively more important than that involving androstenedione to estrone to estradiol.
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PMID:Enzymatic control of estrogen production in human breast cancer: relative significance of aromatase versus sulfatase pathways. 352 46


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