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)

14,15-3H-Norethisterone-4 beta, 5 beta-epoxide, a metabolite of norethisterone, was incubated with several proteins and nucleic acids. After 30 min incubation 0.19 nmol of the epoxide were irreversibly bound per mg albumin which contains free sulfhydryl groups; proteins without SH-groups, such as concanavalin A, gamma-globulin, DNA and RNA, did not irreversibly bind norethisterone epoxide. A superoxide (O2) generating enzyme system comprised of xanthine oxidase and hypoxanthine was capable of catalyzing the irreversible binding of the parent compound, norethisterone, to albumin, indicating that an oxidation product was formed which reacted with the protein. When norethisterone epoxide was incubated for 60 min with hepatic microsomes of rats in absence of NADPH, about 2.0 nmol of the epoxide were irreversibly incorporated per mg microsomal protein. This binding was increased to 5.2 nmol by addition of a NADPH regenerating system. Addition of glutathione and cytosol decreased only the NADPH-dependent protein binding; phenobarbital pretreatment of rats induced this NADPH-dependent binding of norethisterone epoxide to microsomal protein by a factor of 2. In presence of NADPH, binding of the epoxide to microsomal protein depended on substrate concentration used. The results indicate that norethisterone epoxide is able to chemically react with proteins. In addition, hepatic microsomal enzymes convert the epoxide to another metabolite which also can react with proteins.
Steroids 1976 Jan
PMID:Irreversible protein binding of norethisterone (norethindrone) epoxide. 0 5

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

Incubations of tritiated 17alpha-ethynylestradiol (EE2) with liver explants of baboon and mouse showed the primate species to be more efficient in the removal of the ethynyl group. Liver microsomes from sexually immature male and female baboons were then incubated with tritiated EE2 and estradiol (E2). Each hormone bound irreversibly to the microsomal pellet. Addition of glutathione reduced the irreversible or covalent association. Incubations with E2 demonstrated significant conversion to estrone (E1). The EE2 experiments demonstrated a conversion to estrone only in the presence of an NADPH-generating system, and the addition of SKF-525A reduced the conversion of EE2 to E1. The cleavage reaction appears to be an oxidative event.
Steroids 1977 Jul
PMID:Oxidative metabolism and de-ethynylation of 17alpha-ethynylestradiol by baboon liver microsomes. 2 74

A method for the preparation of radioactive estradiol-17 beta, 17-glucosiduronate by incubating 3H-estradiol with rhesus monkey liver microsomal preparation in the presence of uridine diphosphoglucuronic acid is described. Small but significant amounts of the conjugate were also obtained from the 150,00 pellet and cytosol fractions. The addition of NADPH to the incubation media increased the yield of radioactive-estradiol-17 beta, 17-glucosiduronate perhaps by preserving the integrity of the C-17-hydroxyl group. As expected, the effect of the reduced nucleotide was more pronounced in the fractions other than the microsome. The biosynthesized conjugate was isolated and purified by multiple column chromatography and the structure was confirmed by derivative formation, enzyme hydrolysis and crystallization of the aglycone.
Steroids 1977 Aug
PMID:In vitro biosynthesis of radioactive estradiol-17 beta, 17-glucosiduronate by rhesus monkey liver. 2 46

The 5alpha reductase activity ofthe monkey epididymis was studied. The enzyme was found in particulate subcellular fractions, its distribution closely resembling that of the microsomal marker enzyme NADPH: cytochrome c reductase, suggesting an association of 5alpha reductase with membranes of the endoplasmic reticulum. Maximal enzyme activity was found at pH 5.4 and at 32--37 C. The crude nuclear preparation had a Km: 0.315 x 10(-6)M and Vmax: 168 pmoles/mg protein/h. The microsomal enzyme had a Km: 0.243 x 10(-6)M and Vmax: 828 pmoles/mg protein/h. Neither enzyme preparation was affected by addition to the incubation media of dihydrotestosterone (DHT) or 5alpha-androstane-3alpha,17beta-diol. The endogenous androgen concentration in the epididymides of 2 different monkeys, in ng/g wet weight was: DHT 20.81 +/- 1.98; T: 9.0L +/- 2.83; diol: 3.03 +/- 0.41.
Steroids 1978 Jan
PMID:Androgen concentration and partial characterization of 5alpha reductase in the epididymis of the rhesus monkey. 2 92

This study has characterized two new enzymatic hydroxylase activities specific for 5 alpha-androstane-3 beta, 17 beta-diol (3 beta-diol) in the rat ventral prostate: 5 alpha-androstane-3 beta, 17 beta-diol 6 alpha-hydroxylase (6 alpha-hydroxylase) and 5 alpha-androstane-3 beta, 17 beta-diol 7 alpha-hydroxylase (7 alpha-hydroxylase). Both of these irreversible hydroxylase activities require NADPH and are localized in the microsomal fraction of the prostate. The apparent Km for 3 beta-diol is 2.5 microM for both the 6 alpha- and 7 alpha-hydroxylase activities. The apparent Km for NADPH is 7.6 microM for the 6 alpha-hydroxylase and 7.0 microM for the 7 alpha-hydroxylase. The pH optimum for both activities is 7.4. Several steroid inhibitors of these hydroxylase activities in vitro were identified including cholesterol, progesterone, and estradiol. Estradiol was found in vitro to be a noncompetitive inhibitor (Ki = 5 microM). Injection of estradiol into intact male rats, simultaneously receiving exogenous testosterone, also produced a significant lowering of the 6 alpha-plus 7 alpha-hydroxylase activities. Both the 6 alpha- and 7 alpha-hydroxylase were found to be androgen sensitive. Following castration there is a rapid decrease in both activities.
Steroids 1979 Jun
PMID:Characterization of two new enzymatic activities of the rat ventral prostate: 5 alpha-androstane-3 beta, 17 beta-diol 6 alpha-hydroxylase and 5 alpha-androstane-3 beta, 17 beta-diol 7 alpha-hydroxylase. 3 13

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

The in vitro metabolism of 7-3H-5-androstenediol by the pituitary, some brain structures, and ventral prostate of adult castrated male rat was studied. Conversion of 5-androstenediol to radiochemically pure testosterone was demonstrated in all tissues studied in the presence of a NADPH generating system. Formation of dihydrotestosterone and dehydroepiandrosterone was also detected. The higher conversion rates were found in the pituitary, hypothalamus and mesencephalic tegmentum. These results demonstrate the presence of 3beta-hydroxy steroid oxidoreductase, delta4- delta5 isomerase, 5alpha-reductase, and 17beta-ol dehydrogenase in the rat brain which may in part explain the behavioral and brain virilization effects of 5-androstenediol.
Steroids 1977 May
PMID:In vitro conversion of 5-androstenediol to testosterone by the central nervous system and pituitary of the male rat. 14 88

Glucose- 6phosphate dehydrogenase (G-6PDH) stimulation by estradiol- 17beta has been studied in oviduct and liver of Bufa arenarum. OviducalG-6PDH has been found to be stimulated by a single dose of estradiol- 17beta (100 mug/100 g body weight), the stimulation being dependent on season. Hepatic G-6PDH of females is susceptible to hormonal stimulation, without seasonal variation, while in males the enzymatic activity is not modified under the same conditions. The stimulating effect of estrogen on oviducal and hepatic G- 6PDH was inhibited by Actynomicin D. The susceptibility of G- 6PDH to estrogenic action would assure NADPH production, indispensable for the biosynthesis of lipids which are required for cell growth and for hepatic vitellogenesis.
Steroids 1977 Feb
PMID:Effect of estrogens on glucose phosphate dehydrogenase activity of liver and oviduct in the amphibian Bufo arenarum. 40 19

The effect of thiamin deficiency on the metabolism of the oral contraceptive mestranol by female rat liver enzymes was determined. Rats were fed a diet for 3 weeks containing 0, .3, .7, 2.0, or 20 mcg thiamin/gm food before decapitation and extraction of liver microsomes. Mestranol was incubated with 1 ml microsomes from 250 mg liver and the metabolic reaction started by addition of cofactors and NADPH. Liver microsomes from rats fed a thiamin-deficient diet had 3 times the capacity to metabolize mestranol as microsomes from rats fed a thiamin-rich diet. The incremental addition of thiamin to the diet depressed mestranol 0-demethylation, NADPH cytochrome c reductase, and cytochrome P-450 content. Pair-feeding experiments indicate that the carbohydrate portion of the food is responsible for decrease in cytochrome c, while thiamin levels are responsible for changes in the other 2.
Steroids 1977 Aug
PMID:The influence of thiamin deficiency on the metabolism of the oral contraceptive mestranol [3-methoxy-17-ethynyl-1,3,5(10)-estratrien-17 beta-o1] by female rat liver enzymes. 41 82


1 2 3 4 5 6 7 8 9 10 Next >>