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

Epididymal 5alpha reductase activity was found distitributed in the crude nuclear fraction (44 percent) and microsomal fraction (41 percent). Spermatozoa contaminating the nuclear preparation accounted for only 3 percent of its activity. There were no regional differences in the distribution of total 5alpha reductase activity. However, the nuclear enzyme was more active in caput than in other regions. Maximal activity was found at pH 6.2 and at 32 degrees C. Both enzymes had an absolute requirement of reduced dinucleotides. The microsomal preparation could only us NADPH while the nuclear enzyme could use NADPH and NADH. The apparent Km for the microsomal preparation was 0.62 +/- 0.05 X 10(-6)M and Vmax was 555 +/- 38 pmoles/mg protein/hour. The nuclear enzyme presented similar values. The reaction was not inhibited by accumulation of product in the medium, but other steroids such as progesterone, epitestosterone (17alpha-hydroxy-4-androsten-3-one) and 3-oxo-4-androstene-17beta-carboxylic acid were potent competitive inhibitors. The reaction was strongly inhibited by Hg, Zn and Cu. The properties of the epididymal reductase are similar to those of the prostatic enzyme.
Steroids 1977 Jul
PMID:Partial characterization of epididymal 5 alpha reductase in the rat. 2 73

Ecdysone 3-epimerase was partially purified by ammonium sulfate fractionation from the 100,000 g supernate of Manduca sexta midguts. The enzyme converts ecdysone and 20-hydroxyecdysone to their respective 3-epimers, requires NADH or NADPH and O2 for this reaction, and has the following kinetic parameters: for ecdysone, Km = 17.0 +/- 1.4 microM, Vmax = 110.6 +/- 14.6 pmol min-1 mg-1; for 20-hydroxyecdysone, Km = 47.3 +/- 7.5 microM, Vmax = 131.0 +/- 3.5 pmol min-1 mg-1: for NADPH, Km = 85.4 +/- 10.6 microM; for NADH, Km = 51.3 +/- 1.3 microM. The reaction is irreversible and can be inhibited by various ecdysteroids.
Steroids 1979 Nov
PMID:Ecdysone 3-epimerase from the midgut of Manduca sexta (L.). 4 74

After addition of estrone to rat liver slices, a quotient of estradiol/estrone of ca. 0.1 is reached within 1 - 2 min. By additional application of 17 beta-hydroxysteroids this quotient is changed in the direction of estradiol, although the applied concentrations of both steroids are far below the concentration of the cytoplasmic redox couple NADH/NAD. Of all the steroids tested, testosterone had the strongest influence on the quotient, especially in the liver of female rats. This influence is smaller in the livers of male rats and infantile animals. The changing of the E2/E1 quotient by testosterone can be inhibited by the antiandrogen cyproteron acetate. Steroids with hydroxy groups at C-3 or C-20 or high concentrations of non-steroids, which can be oxidized by NAD, change the E2/E1 quotient only minimally. The experiments demonstrate that in liver, the redox couple estradiol/estrone is not in equilibrium with the main redox couple of the cytoplasmic NADH/NAD. Only on account of this fact it is possible that relatively low concentrations of testosterone change the E2/E1 quotient via the C-17 leads to C-17 hydrogen transfer between steroids. Biological consequences are discussed.
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PMID:[Increased estradiol-estrone quotient in rat liver by hydroxysteroids: an effect of the specific hydrogen transfer between steroids]. 16 43

The properties and subcellular distribution of anterior pituitary delta4-steroid (progesterone) 5alpha-reductase, which stimulates the conversion of progesterone to 5alpha-pregnane-3,20-dione, have been investigated utilizing 3H-substrate and a reverse isotopic dilution assay system. The enzymic activity was stimulated by NADPH but not NADH and exhibited a Km of 2.7+/-0.9 times 10(-7) M for progesterone. The substrate specificity of the enzyme for other delta4-3-ketosteroids and the effect of estradiol-17beta were also studied. 20alpha-hydroxy-4-pregnen-3-one was more reactive than progesterone, while testosterone was less reactive. Estradiol-17beta in vitro had an inhibitory effect on the 5alpha-reduction of progesterone. Studies on the subcellular distribution of the 5alpha-reductase activity indicate that the bulk of the activity was widely distributed amongst particulates sedimenting at 1,000, 15,000 and 100,000xg; with the 15,000xg pellet containing the most enzymic activity. The 100,000xg supernatant possessed only a small fraction of the total activity. After further fractionation of the 1,000xg pellet, the activity was distributed equally between the purified nuclear and cell debris-membranes fractions.
Steroids 1975 Jul
PMID:Properties and subcellular distribution of delta4-steroid (progesterone) 5alpha-reductase in rat anterior pituitary. 116 84

The oral administration of indole-3-carbinol (IC), present in cabbage and other members of the Cruciferae family, to female rats almost doubled their ability to convert estradiol to catechol estrogens in the liver. This was determined by the release of 3H from C-2 of the estrogen and also by isolation of the 14C-labeled catechol derivative after incubation with hepatic microsomal fractions. The yield of 4-hydroxyestradiol was also elevated and these effects were similar to those produced by 3-methylcholanthrene (MC), a well-characterized cytochrome P450 inducer. Further evidence for the involvement of a mixed-function oxidase was provided by a 70% to 80% decrease in the yield of 3H2O and water-soluble radioactivity by SKF-525A (0.1 mM) when added to the microsomal fractions isolated from the livers of control or IC-treated rats. In addition, NADPH could not be replaced by NADH in these experiments. Pretreatment with ethionine prevented the increase in estradiol metabolism brought about by oral administration of IC. Both IC and MC inhibited catechol estrogen formation when added directly to the liver microsomal system, confirming earlier findings that in vivo inducers can act as in vitro inhibitors. However, IC was less inhibitory than MC, supporting the theory that IC is converted to a more active product in the stomach. Thus, IC may be conferring protection against estrogen-dependent neoplasia by increasing the hepatic oxidation of estradiol, thereby lowering the amount of available active estrogen.
Steroids 1991 Aug
PMID:Influence of indole-3-carbinol on the hepatic microsomal formation of catechol estrogens. 166 92

In all subcellular pituitary fractions, 3 alpha-hydroxysteroid dehydrogenase (3 alpha-ol dehydrogenase) activity is high (1 to 3 pmol/mg/h) with NADH or NADPH as cofactor, and 3 beta-hydroxysteroid dehydrogenase (3 beta-ol dehydrogenase) activity much lower. The highest activity of the latter (0.15 pmol/mg/h) is detected in cytosol with NADH as cofactor. During sexual maturation, cytosolic (NADH-dependent) 3 alpha- and 3 beta-ol dehydrogenase activities remain constant, whereas the 5 alpha-reductase activity is maximum at 37 days. The levels of different pituitary androgens were evaluated by radioimmunoassay. At 28 days, testosterone level is 4 ng/g of tissue, then after 42 days the level remains between 4.5 and 6 ng/g at a level higher than the DHT level. In all cases during the maturation of the rat, the different 5 alpha-reduced androgens are in the same ratio: DHT greater than 3 alpha-diol greater than 3 beta-diol, and the sum of these three 5 alpha-reduced androgens decreases between the 28th and the 90th day.
Steroids 1989 Jun
PMID:The activity of 3 alpha- and 3 beta-hydroxysteroid dehydrogenases and 5 alpha-reductase, together with androgen levels in male rat pituitary during sexual maturation. 281 53

Prostaglandin H synthase (PHS) from ram seminal vesicle microsomes was found to catalyze the release of tritium (3H) from estradiol (E2) regiospecifically labeled in position C-2 or C-4 of ring A but not from positions C-17 alpha, C-16 alpha, or C-6,7. Formation of 3H2O from ring A of E2 is dependent upon native enzyme supplemented with either arachidonic acid, eicosapentaenoic acid, or hydrogen peroxide and proceeds very rapidly as do other cooxidation reactions catalyzed by PHS-peroxidase. The 3H-loss from ring A of E2 reflecting oxidative displacement of this isotope by PHS increases linearly up to 100 microM under our conditions (8-45 nmol/mg x 5 min). Loss of tritium in various blanks is negligible by comparison. Indomethacin (0.07 and 0.2 mM) inhibited the PHS-dependent release of 3H2O from estradiol but less efficiently than it inhibited DES-cooxidation measured in parallel incubations under similar conditions. Addition of EDTA (0.5 mM) had no effect on the regiospecific transfer of 3H from E2 or on DES-oxidation; ascorbic acid (0.5 mM) or NADH (0.33 mM) clearly inhibited both reactions and to a similar extent. These data suggest that estradiol-2/4-hydroxylation can be catalyzed by PHS in vitro probably via its peroxidase activity and point to PHS as an enzyme that could contribute to catechol estrogen formation in vitro by tissue preparations in the presence of unsaturated fatty acids or peroxides.
Steroids 1987 Jun
PMID:Prostaglandin H synthase catalyzes regiospecific release of tritium from labeled estradiol. 313 54

Flutamide (0.5 mM) decreased in vitro the activity of NADH-5 alpha-reductase (substrate testosterone) in liver homogenate of male and female rats, whereas no change of activity of NADPH-5 alpha-reductase was observed. NADH- and NADPH-5 beta-reductase activity increased only in liver of female, but not of male rats. NAD+-3 beta-hydroxysteroid dehydrogenase and NAD+-3 alpha-hydroxysteroid dehydrogenase (substrate 5 alpha-dihydro-testosterone) in liver homogenate from female rats were inhibited by flutamide (0.5 mM), whereas the activity of NADP+-3 alpha-hydroxysteroid dehydrogenase (substrate 5 alpha-dihydrotestosterone) and of NAD+-3 alpha-hydroxysteroid dehydrogenase (substrate 5 beta-dihydrotestosterone) increased in presence of flutamide. The activity of NADH- and NADPH-5 alpha-reductase decreased after flutamide administration to female rats at a dose of 5 mg per day for 7 days.
Steroids 1987 Jun
PMID:Effect of flutamide on 5 alpha-reductases, 5 beta-reductases, and 3-hydroxysteroid dehydrogenases in rat liver. 348 96

Although it is well established that ethanol suppresses gonadotropin- and cAMP-stimulated testicular steroidogenesis, there is not good agreement on two issues: which is the step in testosterone's biosynthetic pathway affected by ethanol; and the role of alterations in the NAD+/NADH ratio in ethanol's effects. In these studies, we have identified major differences between in vivo and in vitro approaches, which have previously been considered as totally equivalent experimental paradigms, which could explain these discrepancies. Under in vitro conditions, we observed that ethanol selectively inhibited the conversion of androstenedione to testosterone, but that it had a much more general effect under in vivo conditions. In addition, in agreement with other studies, NAD+ overcame ethanol's effects on testicular steroidogenesis in vitro, but only when labeled or unlabeled pregnenolone was added. In the absence of added pregnenolone, NAD+ was not effective in preventing ethanol's effects. Our results, thus, indicate that the differences which currently exist in the literature may be explained by the indiscriminate usage of in vivo and in vitro techniques.
Steroids 1982 Nov
PMID:Ethanol-induced reductions in testicular steroidogenesis: major differences between in vitro and in vitro approaches. 631 43

The ability of NADH to function as an alternative cofactor for the support of estrogen biosynthesis was validated. NADH supported rates of aromatization of up to 80% of those obtained with NADPH, with an apparent Km of 0.70 mM, and stimulated the NADPH-supported reaction only when supplies of the normal cofactor were limiting, both additive and synergistic effects being observed. NADH-supported aromatization was inhibited competitively by NADP+ and 2'-AMP with Ki values of 5 microM and 22 microM, respectively. Support by both cofactors was lost in parallel with the selective removal of NADPH-cytochrome c reductase from microsomes by graded subtilisin treatment. NADH-supported aromatization was differentiated from NADPH-supported aromatization by its sensitivity to inhibition by NAD+ and its response to changes in ionic strength. NADH appears to function, at high concentrations, as a surrogate for NADPH at the reduced nucleotide-binding site of NADPH-cytochrome c reductase but additional roles for NADH are also suggested both when acting alone and as a supplement to NADPH. A common oxidase (cytochrome P-450) appears to catalyze both NADH- and NADPH-supported aromatization.
Steroids 1983 Jul
PMID:The roles of NADH in the support of steroid aromatization by human placental microsomes. 642 72


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