Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
 7,802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An attempt to confirm the effect of oral contraceptives (OCs) on the plasma dehydroepiandrosterone sulfate (DHEAS) and to explore the biochemical site of their action is presented. 89 women taking estrogen-containing OCs for 6 months or longer and 47 controls were studied. Both groups were of similar age, and with regular menstrual cycles. OCs used were Ovral (ethinyl estradiol, 50 mcg, norgestrel, .05 mg), Demulen 50 (ethinyl estradiol, 50 mcg; ethynodiol diacetate, 1 mg), and Ortho-Novum 1/50 (mestranol, 50 mcg; norethindrone, 1 mg). A single sample of plasma was made from the heparinized blood taken between 7-8 a.m. between Days 15-21 of a contraceptive treatment cycle in the experimental group and between Days 15-21 of a menstrual cycle in the control group. The results of the plasma DHEAS, DHEA, and androstenedione assays showed that all 3 OC preparations caused reductions in the androgenic steroids when compared with the controls. Results of statistical comparisons between the different OCs did not indicate if ethinyl estradiol or mestranol exerted a greater effect. Concentrations of delta-5-P and 17-delta-5-P were found to be lower in the experimental cases than in the controls. It is concluded that OCs cause a decrease in plasma DHEA, DHEAS, and androstenedione, with 1 possible mechanism being the inhibition of delta-5-P synthesis from cholesterol.
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PMID:Effect of oral contraceptives on plasma androgenic steroids and their precursors. 14 99

17 beta-Hydroxysteroid dehydrogenase activity towards estradiol-17 beta has been demonstrated in the 105,000 x g supernatant of rabbit uterus. Hydroxylapatite chromatography of the enzyme activity isolated by ammonium sulfate precipitation, gel filtration and DEAE-cellulose chromatography yielded a single 17 beta-hydroxysteroid dehydrogenase activity. Further purification of the enzyme preparation by isoelectric focusing resulted in multiple peaks of activity. The molecular weight of the enzyme, caculated from mobility data on Sephadex gel, is approximately 64,000. Some properties of partially purified 17 beta-hydroxysteroid dehydrogenase activity have been studied. Estradiol-17 beta reacts at a faster rate than testosterone. The Km for estradiol is 4.16 x 10(-5) mol/l for the NAD-linked enzyme activity and 4.37 x 10(-5) mol/l when NADP as cofactor was used. The ratio of the maximal velocity for NADP to that for NAD was 1.42. The pH-optimum for estradiol appears between 9.5 and 10.5 and for estrone between 5.5 and 6.5. The enzyme appears to be of the sulfhydryl type.
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PMID:Purification and properties of the soluble 17 beta-hydroxysteroid dehydrogenase of rabbit uterus. 16 Jun 96

17beta-[6,7-3H]Estradiol (E2) was incubated with slices and homogenates of adult human renal tissue. The metabolites formed were identified by chromatography on DEAE-Sephadex, thin layer chromatography and crystallization with carrier steroids or steroid derivatives. The major metabolites formed by slices were estradiol-17-glucuronide (E217G), estrone sulfate and estradiol-3-sulfate. This is the first report of in vitro synthesis of estrogen sulfates by adult renal tissue. Minor quantities of the 3-glucuronides of estrone and estradiol were also found. An oxygen atmosphere appeared to stimulate the production of E217G. A time study with tissue slices showed similarities between the in vitro pattern of glucuronide synthesis and the excretion pattern of these compounds seen in earlier in vivo studies. Homogenates fortified with uridine diphosphoglucuronic acid formed the same pattern of glucuronide products but in lesser amounts. No sulfates were formed under these conditions. Testosterone did not act as a substrate in the experimental conditions used.
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PMID:In vitro synthesis of estrogen glucuronides and sulfates by human renal tissue. 16 18

We have studied the binding of 125I-human growth hormone (hGH) to crude 100,000 X g membrane preparations from rat liver, and have studied factors which might regulate the capacity and affinity of hGH binding sites. Membrane preparations have livers of pregnant rats bound between 8% and 18% of the 125I-hGH initially added, and 70%-80% of that bound was displaced by 1 mug of unlabeled hGH. Humans prolactin (hPrl) displaced 125 I-hGH in a manner parallel to hGH itself but with about one-third the potency. Ovine, porcine, and rat Prl, and rat and bovine GH were much less effective. Scatchard analysis of specific hGH binding by a variety of different rat liver membrane preparations revealed a single order of binding site in each case with a binding affinity of 0.93-1.62 X 10(-9) M-1. Membranes from pregnant rats had twice the binding capacity of membranes from nonpregnant female rats, and about six times the capacity of sites present in preparations from normal adult male rats and hypophysectomized (Hx) male or female rats. Female or male rats with extremely high circulating GH an Prl levels, due to the presence of transplantable GH/Prl secreting pituitary tumors showed a significantly greater binding capacity than did the pregnant rats. Estradiol (E2) treatment (25 mug/day for 10-12 days) of normal male rats led to an increase in specific hGH binding. Treatment of hypophysectomized male rats with bovine GH (100 or 500 mug/day) +/- E2 (25 mug/day) for 5-10 days stimulated both body weight gain and the incorporation of sulfate by cartilage from the treated rats, but no significant increase was observed in the characteristics of 125I-hGH binding. These results indicate that high levels of E2, GH, and/or Prl play an important role in the regulation of hGH binding sites in rat liver membranes. The restoration of binding sites in liver from hypophysectomized rats, however, apparently requires additional factors which are as yet unidentified. The role of the hGH binding sites in the physiologic actions of GH also remains to be determined.
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PMID:Pituitary regulation of human growth hormone binding sites in rat liver membranes. 17 42

The acute and chronic effects of estradiol (E2) on the serum levels of four delta5,3-beta hydroxysteroids and their four delta4, 3-keto products were studied in four ovariectomized women with and without adrenal stimulation by ACTH. Six hour infusions of saline and of synthetic 1-24 ACTH were administered and later repeated with a two hour infusion of E2 50 mug/h. The patients were then given 50 mug of ethinyl estradiol (EE2) p.o. for 4 to 6 weeks and the control and ACTH infusions were again repeated. Levels of pregnenolone3 (Pe), 17alpha-hydroxypregnenolone (17 Pe), progesterone (Po), 17alpha-hydroxyprogesterone (17 Po), dehydroepiandrosterone (DHEA), androstenedione (Adione), androstenediol (Adiol), and testosterone (T), as well as cortisol and DHEA-sulfate were measured by radioimmunoassay on serum samples taken at 1200 and 1300 h. There was no significant effect of E2 or EE2 in the doses administered with or without exogenous ACTH on 3 betaOHSD activity as reflected in absolute steroid levels or in the ratio of concentrations of each delta5:delta4 steroid pair. During the 4th and 5th hour of ACTH infusion, the plasma level of 17 Pe (mean 22.5-fold stimulation) was most elevated, followed by 17 Po (12.5-fold), Pe (10-fold), cortisol (5.9-fold) and Po (4.5-fold), with smaller increases for the other steroids. These results, as well as the pattern of change in plasma levels in one of the subjects in whom fifteen minute samples were measured, provide further evidence suggesting that the major pathway for cortisol biosynthesis in vivo proceeds from Pe via 17 Pe, and not via Po.
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PMID:Effects of estrogens on adrenal 3 beta-hydroxysteroid dehydrogenase in ovariectomized women. 18 11

Many previous studies have demonstrated effects of gonadal steroids on adrenal weight in the rat. Most of these effects are indirect, depending upon alterations in the pituitary-adrenal axis for their expression. In this study we have attempted to examine the direct effects of gonadal steroids on adrenal weight in the rat. This was done using hypophysectomized, castrated male rats receiving ACTH replacement, a model which excludes pituitary-adrenal feedback effects. Estradiol-treated rats did not differ from controls, whereas testosterone-treated rats exhibited a small but statistically significant decrease in adrenal weight. As a first step in exploring the mechanism of this androgen effect, we have identified a specific dihydrotestosterone-binding protein in the rat adrenal gland. A single class of high affinity (Kd = 0.6-2.0 x 10(-8) M), saturable (28 fmol/mg cytosol protein), cytoplasmic binding sites was found using both protamine sulfate precipitation and dextran-coated charcoal assays. The specificity, sedimentation coefficient on sucrose gradient, and sensitivity to sulfhydryl reagents and heat of this dihydrotestosterone-binding protein are typical of the cytoplasmic androgen receptor from other androgen target tissues such as prostrate. We conclude that testosterone can decrease rat adrenal weight directly, and that the mechanism may involve a high affinity binding protein, as has been shown in other androgen-responsive systems.
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PMID:Rat adrenal androgen receptor: a possible mediator of androgen-induced decreased in rat adrenal weight. 21 67

Estradiol 17beta-dehydrogenase from human placenta has been crystallized by a new technique, herein referred to as electrophoretic diffusion. This is the first crystallization of an enzyme from human placenta as well as the first crystallization of any steroid-converting enzyme of human source. A solution of the enzyme (specific activity 7.1 units/mg) in 1.5 ml of Tris-barbituric acid buffer, pH 7.0, containing 20% glycerol as stabilizer, was placed in an electrophoresis tube and the tube was closed at both ends with a dialysis membrane which permits the passage of substances of molecular weight less than 18,000. The tube was placed in a gel electrophoresis apparatus and the reservoirs filled with the Tris-barbituric acid buffer. A potential of 100 V was applied for 12 hours, then raised to 200 V for another 12 hours, and finally to 300 V until opalescence appeared at the bottom of the tube. Activity measurements showed that more than 90% of the enzyme had concentrated in the bottom 0.15-ml portion of the solution. When this section of the solution was removed and kept overnight at 4 degrees, gross and microscopic examination revealed a heavy crop of crystals which possessed a specific activity of 7.2 units/mg. The specific activity remained constant throughout three recrystallizations. The crystalline enzyme displayed a single band by analytical and sodium dodecyl sulfate-polyacrylamide gel analysis. Crystals of enzyme of high specific activity could also be obtained from an enzyme sample initially possessing a specific activity of only 4.5 units/mg. The new technique should be appliable for the crystallization of other labile enzymes and receptor proteins which have so far resisted crystallization by conventional methods.
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PMID:Crystallization of human placental estradiol 17beta-dehydrogenase. A new method for crystallizing labile enzymes. 93 3

A fundamental study of testosterone-estradiol binding globulin (TeBG) activity for estradiol-17beta was investigated by equilibrium dialysis. In addition, the interaction of TeBG activity for estradiol and estradiol metabolism during a menstrual cycle and in hyperthyroidism was attempted to elucidate. Estradiol in plasma and 24 hrs urine was measured by radioimmunoassay. TeBG binding capacity (TBC) was measured by ammonium sulfate method and associate constant (Ka) of TeBG for estradiol was estimated by equilibrium dialysis. 1. In several pooled plasmas, the mean Ka of TeBG for estradoil was 1.25 X 10(8) L/M at 4 degrees C and 0.78 X 10(8) L/M at room temperature. The Ka decreased with increasing temperature and could not be determined with a sufficient accuracy at 37 degrees C. The mean TBC was 4.4 X 10(-8) M/L. 2. TBC and Ka of TeBG for estradiol during the normal menstrual cycle of a woman were fairly unchanged. The unconjugated estradiol value in urine showed the same biphasic pattern with a midcycle peak as that of the unconjugated estradiol value in urine. 3. A normal man was induced hyperthyroidism with a administration of triiodothyronine. The treatment of triiodothyronine caused a remarkable increase of TBC, but no changes of Ka of TeBG for estradiol and unconjugated estradiol values in plasma and urine. From these results it was suggested that the rate of metabolism of estradiol increased in hyperthyroidism.
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PMID:[Studies of binding of testosterone-estradiol binding globulin for estradiol-17beta (author's transl)]. 98 59

3H and 14C-Labeled estrone, estradiol, and estrone sulfate were infused at constant rates into brachial arm veins of normal men. In any one experiment, subjects generally received two estrogens, one 3H-labeled and one 14C-labeled. During the infusions, blood samples were obtained from the brachial artery, a deep vein draining primarily muscle and a superficial vein draining primarily adipose tissue of the arm contralateral to the infusion. In 11 men the mean +/- SE value for the metabolism of estrone by muscle, rho1,0A,M(rho1,0A,M = fraction of estrone in arterial blood which is metabolized by muscle) is 0.17 +/- 0.02 which is not (P greater than 0.1) significantly different from the mean +/- SE value for the metabolism of estrone by adipose tissue, rho1,0A,AT, 0.22 +/- 0.02. Both tissues convert estrone to estradiol, rho1,2A,M(rho1,2A,M = fraction of estrone in arterial blood which is measured as estradiol in venous blood draining muscle) is 0.026 +/- 0.005 and rho1,2A,AT is 0.022 +/- 0.005. Both tissues metabolized estradiol, rho2,0A,M = 0.09 +/- 0.01 and rho2,0A,AT = 0.12 +/- 0.03, and for each tissue the metabolism of estradiol was significantly less than that of estrone (P less than 0.01). Estradiol was converted to estrone by both tissues; rho2,1A,M = 0.007 +/- 0.003 and rho 2,1A,AT = 0.017 +/- 0.003. For estrone sulfate, tissue metabolism could be demonstrated in only 2 of 5 infusions; the values being 0.04 and 0.03, and 0.04 and 0.03 in muscle and adipose tissue, respectively. In only 1 of 3 infusions was evidence obtained for the conversion, by muscle, of estrone sulfate to estrone, rhoS,1A,M = 0.003 and only in one of the 5 subjects was adipose tissue active in this conversion. In no instance were we able to show conversion of estrone sulfate to estradiol by either tissue. In only 1 of 3 infusions could we measure demonstrable conversion of estrone to estrone sulfate by adipose tissue, rho1,SA,AT = 0.02, and we could not demonstrate conversion of estrone to estrone sulfate by muscle or of estradiol to estrone sulfate by either tissue. Both muscle and adipose tissue metabolize and interconvert the free estrogens, estrone and estradiol. The total metabolism by both tissues accounts for 5-10% of the overall metabolic clearance rate of each steroid. The formation of estrone sulfate from estrone and estradiol and the hydrolysis of estrone sulfate occurs to only a minor extent in these tissues.
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PMID:In vivo studies on the metabolism of estrogens by muscle and adipose tissue of normal males. 99 16

17beta-[6,7- 3H]Estradiol was incubated with adult human liver slices in Krebs-Ringer phosphate buffer containing glucose. Of the identified 3H recovered, 51-76 percent consisted of estrone-3-sulfate (E13S) and 17 beta-estradiol-3-sulfate (E23S). E13S was the main metabolite and was found in both tissue and medium. E23S was present only in the medium. Minor amounts of estrogen glucuronides were formed. When a human liver homogenate was incubated with [3H]E2 in a medium fortified with excess uridine diphosphate glucuronic acid only some 4 percent of conjugation with glucuronic acid was observed. It is suggested that human liver favors sulfurylation as the conjugating mechanism for E2 and E1.
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PMID:In vitro metabolism of 17beta-estradiol by human liver tissue. 118 Oct 8


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