Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steroid sulfatase of human placenta has been solubilized by treatment of the microsomal fraction with an amphoteric surface active agent, Miranol H2M and ultrasound. Criteria of solubility include non-sedimentation of the activity following centrifugation at 160,000 x g, its retention on Sepharose 6B and a single peak of activity after polyacrylamide gel electrophoresis. Enzyme activity was located in the same gel fractions for the two substrates tested; cholesterol sulfate and dehydroisoandrosterone sulfate. The addition of dithiothreitol was found necessary to maintain the stability of the enzyme indicating the presence of sulfhydryl groups in the molecule. A molecular weight of approximately 330,000 has been estimated from the elution volume of the enzyme system on a column of Sepharose 6B. It is believed that this protein represents a sulfatase enzyme complex composed of subunits with different specificities. From kinetic studies, a Km of 6.2 x 10(-5)M for the cleavage of dehydroisoandrosterone sulfate and a Km of 2 x 10(-6)M for the cleavage of cholesterol sulfate have been calculated.
Steroids 1978 Jun
PMID:Solubilization and partial purification of steroid sulfatase of human placenta. 69 67

Different cellular fractions of guinea-pig placenta were incubated in the presence of (7n-3H) testosterone. Microsomal aromatization of 3H-testosterone into estrone and estradiol-17beta was demonstrated in the presence of NADPH. The predominance of estrone after incubation with 17beta-hydroxylated precursors, (7n-3H) testosterone and (6,7-3H) estradiol-17beta, indicate that there is a microsomal 17beta-hydroxysteroid dehydrogenase activity. In this report, cytosolic sulfurylation of estrogens is demonstrated. This latter activity represents a quite original characteristic of the placental metabolism of estrogens in guinea-pigs. In contrast with the human placenta where there is considerable sulfatase activity, the guinea-pig placenta can sulfurylate estrogens.
Steroids 1978 Oct
PMID:Conversion, in vitro, of (7n-3H) testosterone to estrone and estradiol-17beta and their 3-sulfate conjugate by the guinea-pig placenta. 71 21

Lipid content and steroid sulfatase activities were determined in liver and uterus microsomes of non-pregnant guinea pigs. The results were compared with values obtained in pregnant and cortisol-treated animals. Steroid sulfatase activities were always higher in pregnant animals, and we supposed that the increase in circulating cortisol in pregnant guinea pigs before parturition has an influence on the membrane-bound sulfatase activities. Sulfatase activities were identical in cortisol-treated and untreated non-pregnant females, although cortisol induced changes in microsomal lipid composition. These results lead us to three conclusions: in intact female guinea pigs, cortisol induces variations in the lipid content of uterus and liver microsomes, especially in the cholesteryl sulfate to phospholipid ratios; the variations of the lipid composition in pregnant animals do not appear to be cortisol-dependent; membrane-bound steroid sulfatase activities are not directly influenced by the lipid composition of microsomes.
Steroids
PMID:Lack of correlation between steroid sulfatase activities and lipid content in uterus and liver microsomes of guinea pigs. 348 88

Estrone and dehydroepiandrosterone (DHEA) sulfatases were studied in livers of normal and cirrhotic men. Their Km were 3.2 microM and 1.2 microM respectively. The microsomal sulfatases were solubilized by Miranol H2M and ultrasound. After gel filtration, the soluble material gave a single peak of activity for both substrates with a molecular weight of approximately 330,000. In terms of pmol of product.min-1 per mg of fresh tissue, the mean (+/- SD) values of estrone and DHEA sulfatase activities were lower in cirrhotic livers [(n = 7) (4.09 +/- 2.90 and 0.38 +/- 0.20)] than in normal livers [(n = 13)(8.29 +/- 4.00 and 0.69 +/- 0.20)]. The differences were statistically significant : p less than 0.03 for estrone sulfatase and p less than 0.01 for DHEA sulfatase. In cirrhotic men, the mean level of plasma estrone is increased whereas that of estrone sulfate is decreased. The variations may be related to the decrease of serum albumin in cirrhotic subjects.
Steroids 1984 Feb
PMID:Steroid sulfatase activities in normal and cirrhotic livers and plasma levels of estrone sulfate, estrone and estradiol-17 beta in men. 609 55

Using microsomes isolated from term human placentae kinetic analyses of each of the enzymes involved in estrogen synthesis from dehydroepiandrosterone sulfate have been carried out and the following parameters were found: sulfatase, Michaelis-Menten constant (Km) = 16,000 +/- 5,000 nM, maximum velocity (Vm) = 2.0 +/- 0.5 nmol X min-1 X mg protein-1; 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), Km = 15 +/- 3 nM, Vm = 1.8 +/- 0.4 nmol X min-1 X mg protein-1; aromatase, Km = 14 +/- 4 nM, Vm = 0.12 +/- 0.02 nmol X min-1 X mg protein-1. From these values one can predict that, theoretically, the rate-limiting enzyme in estrogen synthesis from dehydroepiandrosterone sulfate (DS) should change from the sulfatase at low concentrations of substrate to the aromatase at higher concentrations. In order to test this hypothesis we developed a system which allowed the formation of estrogens from DS, dehydroepiandrosterone, and androstenedione to be measured and the appropriate intermediates to be isolated. The sulfatase was found to be rate limiting at concentrations of DS below 2 microM and the aromatase was found to be rate limiting at higher concentrations. These data may explain why previous perfusion studies of human placentae indicated the sulfatase was the rate-limiting enzyme in estrogen synthesis yet in vitro studies found that it was the aromatase. Steroids previously shown to inhibit the 3 beta-HSD were examined for their ability to inhibit the formation of estrogens from DS. Although 3 beta-HSD activity was markedly inhibited this had little effect on the overall conversion of DS to estrogens, until high concentrations of inhibitors were used. The data also underline the importance of studying enzyme systems rather than single enzymes when studying steroid synthesis.
 ...
PMID:Kinetic studies on the formation of estrogens from dehydroepiandrosterone sulfate by human placental microsomes. 623 32

Steroid acid esters, synthesized by modifying the 17-ketol side chain of prednisolone, were tested for their in vitro ability to stabilize heavy mitochondrial lysosomes prepared from rat liver. Membrane stabilization was determined by assessing capability of steroids to decrease extrusion of the marker enzymes (acid phosphatase, beta-glucuronidase and aryl sulfatase) from lysosomes incubated in hypo-osmotic sucrose-Tris acetate buffer. Results indicated that prednisolone (1) significantly inhibited the lysosomal release of acid phosphatase as did the new anti-inflammatory steroid, methyl 20-dihydroprednisolonate. Methyl prednisolonate exhibited weak membrane stabilization capacities and 20-dihydroprednisolonic acid, a metabolic product of methyl 20-dihydroprednisolonate, showed virtually no membrane stabilization.
Steroids 1981 Oct
PMID:Stabilization of rat liver lysosomes by new anti-inflammatory steroids in vitro. 689 65

Estrone sulfate levels were measured in the plasma of 63 postmenopausal women. The assay method involved prior extraction of the free estrogens, enzyme hydrolysis of the estrone sulfate with sulfatase and radioimmunoassay of the estrone liberated. The plasma levels ranged from 37 to 320 pg/ml (expressed as free estrone) with a mean value of 178 +/- 79 pg/ml. As observed in premenopause, estrone sulfate is quantitatively the most important circulating estrogen in postmenopausal women.
Steroids 1980 Feb
PMID:Plasma estrone sulfate levels in postmenopausal women. 737 17

The high serum concentration of estrone sulfate and the presence of estrone sulfatase in breast tumors constitute an important mechanism of local synthesis of estrogens in the tissue. Thus, inhibitors of estrone sulfatase may be effective in the treatment of estrogen-dependent breast cancer. In this study, we synthesized several isostructural analogs of estrone sulfate (estrone-3-methylsulfonate, estrone phosphate, 3-desoxyestradiol-3-methylenesulfonate, and 3-desoxyestrone-3-methylenesulfonate) and tested them on human placental sterylsulfatase. The results were (i) The Ki of 3-desoxyestrone-3-methylenesulfonate 12 and 3-desoxyestradiol-3-methylenesulfonate 7 are more than 100-fold higher than the Ki or KM values for estrone sulfate, (ii) As compared to estrone sulfate, the Ki value for estrone-3-methylsulfonate 2 is about 30-fold higher, while estrone phosphate 3 is bound by the sulfatase with roughly the same affinity as estrone sulfate. The results shed some light on the electronical and sterical requirements for high affinity binding to the enzyme.
Steroids 1995 Mar
PMID:Estrone sulfate analogs as estrone sulfatase inhibitors. 779 36

The synthesis and biochemical evaluation of estrone sulfatase inhibitors are described. Inhibitors were designed through modifications of the substrate estrone sulfate. An in vitro assay using the microsomal fraction isolated from human term placenta was used to evaluate sulfatase inhibitory activity. All the inhibitors (except sulfonyl chloride analog) exhibited low inhibitory activities in the screening assay. Sulfonyl chloride analog is a strong inhibitor, which caused 91.5% inhibition of the enzymatic activity at 300 microM.
Steroids 1993 Mar
PMID:Synthesis and biochemical studies of estrone sulfatase inhibitors. 847 13

The spontaneously hypertensive rat (SHR) has a Y chromosome locus that increases blood pressure. This locus requires an androgen receptor and testosterone for maximum expression. Steroid sulfatase (STS) catalyzes the conversion of steroid sulfates to their active nonconjugated form. In some mammals the steroid sulfatase locus (Sts) is on the Y chromosome, although the rat Sts is on the X chromosome. We measured STS activity levels in SHR and normotensive Wistar Kyoto (WKY) males. SHR had significantly higher STS activity in testes, adrenal gland, liver, and hypothalamus. The Km values for STS in the two strains were not significantly different; thus, activity differences were likely due to differences in enzyme amounts. STS activity was measured in the backcross strains SHR/y and SHR/a to test and/or confirm a Y chromosome influence on STS. STS activity levels in these strains were intermediate between those of SHR and WKY. Because the blood pressures of SHR/y and SHR/a were also intermediate between SHR and WKY, the STS activity could be a secondary response to the hypertension. An alternative hypotheses is that a regulatory locus in addition to the structural locus is responsible for STS activity levels, and this regulatory locus is on the rat Y chromosome. Further study is needed to discriminate between these possibilities, and until the second hypothesis can be eliminated, the Sts locus or its modifier loci remain a potential component of the Y chromosome hypertensive locus.
Steroids 1995 Oct
PMID:Steroid sulfatase and the Y chromosome hypertensive locus of the spontaneously hypertensive rat. 853 76


1 2 3 4 Next >>