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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolism of C26 bile alcohols in the bullfrog, Rana catesbeiana, was studied. [24-14C]-24-Dehydro-26-deoxy-5 beta-ranol (3 alpha,7 alpha,12 alpha-trihydroxy-27-nor-5 beta-cholestan-24-one) was chemically synthesized from [24-14C]cholic acid and incubated with bullfrog liver homogenate fortified with NADPH. 24-Dehydro-26-deoxy-5 beta-ranol was shown to be converted into both 26-deoxy-5 beta-ranol and 24-epi-26-deoxy-5 beta-ranol [(24S)- and (24R)-27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24-tetrols] in addition to 5 beta-ranol [(24R)-27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,26-pentol], which is the major bile alcohol of the bullfrog. [24-3H]-26-Deoxy-5 beta-ranol and [24-3H]-24-epi-26-deoxy-5 beta-ranol were prepared from 24-dehydro-26-deoxy-5 beta-ranol by reduction with sodium [3H] borohydride and administered respectively to two each of four bullfrogs by intraperitoneal injection. After 24 h, labeled 5 beta-ranol was isolated from the bile of the bullfrogs that received [24-3H]-26-deoxy-5 beta-ranol. In contrast little if any radioactivity could be detected in 5 beta-ranol or its 24-epimer after administration of [24-3H]-24-epi-26-deoxy-5 beta-ranol.
Steroids
PMID:Metabolism of C26 bile alcohols in the bullfrog, Rana catesbeiana. 314 52

The inhibition of human prostatic 5 alpha-reductase by androstenedione (A), 4-hydroxyandrostenedione (4-OH-A), and 4-methoxyandrostenedione (4-MeO-A) was studied. All three steroids inhibited 5 alpha-reductase in a concentration-dependent manner. The inhibition was competitive with respect to testosterone and non-competitive with respect to NADPH, indicating that these compounds inhibit 5 alpha-reductase by acting as alternative substrates. Ki values obtained were in the range 0.21-0.3 microM (A), 1.01-2.04 microM (4-OH-A), and 10.2-28.3 microM (4-MeO-A). Thus the two derivatives of androstenedione are poor inhibitors of 5 alpha-reductase and appear to have limited clinical potential.
Steroids 1988 Sep
PMID:A kinetic analysis of the inhibition of human prostatic 5 alpha-reductase by 4-hydroxyandrostenedione and related steroids. 325 25

A microsomal fraction of testicular tissue from a patient with prostatic carcinoma was incubated with [4-14C]pregnenolone in the presence of an NADPH-generating system for different periods of time. The metabolites were separated by Sephadex LH-20 column chromatography and then identified by thin-layer chromatography, radio-gas chromatography, and crystallization studies. Pregnenolone was converted to a major metabolite, 5-androstene-3 beta,17 beta-diol via 17-hydroxypregnenolone and then dehydroepiandrosterone. Another major metabolite was 5,16-androstadien-3 beta-ol, which increased with the time of incubation and accumulated in the incubation medium. After 120 min of incubation, 34.6% of the precursor was converted to 5-androstene-3 beta,17 beta-diol and 15.1% to 5,16-androstadien-3 beta-ol. In addition to the above-mentioned steroids, 16 alpha-hydroxypregnenolone, 5-pregnene-3 beta,20 alpha-diol, and 5-androstene-3 beta,17 alpha-diol were identified as minor metabolites of pregnenolone. From these results it was concluded that human testicular microsomes possess enzymic activities for the synthesis of 5,16-androstadien-3 beta-ol, as well as androgens from pregnenolone.
Steroids 1988 Sep
PMID:Formation of 5,16-androstadien-3 beta-ol from pregnenolone in human testicular microsomes. 325 29

2 alpha-Bromoacetoxy (II), 6-bromoacetoxy (VII and X), and 19-bromoacetoxy (XII) derivatives of androstenedione and 17 beta-bromoacetoxy compounds (III, IV, XIII-XVI) were synthesized as potential affinity-labeling reagents for aromatase. 6 alpha-Bromoacetoxy derivative VII was the most potent inhibitor of human placental microsomal aromatase activity among this series. Its inhibitory activity was higher than that of the parent 6 alpha-hydroxy compound V, although other bromoacetates showed weaker inhibition of aromatase than the corresponding alcohols. The bromoacetates (except the 6 beta-bromoacetate X) inhibited aromatase activity in a time-dependent manner in the absence of NADPH, and the enzyme inactivation was blocked by the addition of androstenedione to the incubates. Kinetic analysis of the time- and concentration-dependent inhibition by the 6 beta-bromo-17 beta-bromoacetoxy compound XV gave an apparent Ki of 25 microM and kinact of 0.027 min-1.
Steroids
PMID:Synthesis and evaluation of bromoacetoxy 4-androsten-3-ones as active site-directed inhibitors of human placental aromatase. 344 87

A kinetic analysis of the 5 alpha-reductases from human liver and prostate is presented. Human prostatic 5 alpha-reductase follows an ordered sequential mechanism in which NADPH binds first followed by testosterone. The order of release of products is DHT followed by NADP+. The apparent Km of prostatic 5 alpha-reductase for testosterone is 0.0339 +/- 0.006 microM, while the apparent Km for NADPH is 2.52 +/- 0.65 microM. Human liver 5 alpha-reductase also follows a sequential mechanism. The apparent Km of the liver enzyme is 0.110 +/- 0.08 microM; the apparent Km for NADPH is 6.2 +/- 0.6 microM. The fact that both the liver and prostatic 5 alpha-reductases have a sequential kinetic mechanism rules out the possibility that the reduction of testosterone to dihydrotestosterone involves an electron transport system as previously proposed.
Steroids
PMID:A kinetic analysis of the 5 alpha-reductases from human prostate and liver. 345 48

3 beta,20 alpha-Hydroxysteroid oxidoreductase has been isolated from ovine fetal blood by a 2,370-fold purification scheme of ammonium sulfate fractionation, calcium phosphate gel adsorption, affinity chromatography, and fast performance liquid chromatography. A new high performance liquid chromatography-based assay for measuring 20 alpha-reductase activity is described. The enzyme is a monomer with a molecular weight of 35,000 and uses NADPH as a cofactor for reductase activity. It reduces progesterone to 4-pregnen-20 alpha-ol-3-one or 5 alpha-dihydrotestosterone to 5 alpha-androstan-3 beta,17 beta-diol with kinetic characteristics of Km = 30.8 microM and Vmax = 0.7 nmol min-1 (nmol of enzyme)-1 or Km = 74 microM and Vmax = 1.3 nmol min-1 (nmol of enzyme)-1, respectively. 5 alpha-Dihydrotestosterone competitively inhibits 20 alpha-reductase activity with a Ki value of 102 microM.
Steroids 1987 Jun
PMID:Isolation of 3 beta,20 alpha-hydroxysteroid oxidoreductase from sheep fetal blood. 348 95

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

The conversion of a molecule of 19-oxoandrost-4-ene-3,17-dione [1a] to estrone [2a] by human placental aromatase requires a molecule of oxygen and of NADPH. An atom of this molecule of oxygen is incorporated into the extruded formic acid derived from C-19 of [1a]. It was proposed that the O2 is utilized for the enzymatic 2 beta-hydroxylation of [1a] and the released intermediate 2 beta-hydroxy-19-oxoandrost-4-ene-3,17-dione [5a] aromatized nonenzymatically. Should [5a] be an obligatory intermediate of estrogen biosynthesis, then all the oxygen of its 2 beta-hydroxyl must be incorporated into the extruded formic acid. We have previously synthesized [2 beta-18O; 19-3H] [5c] and proved that none of its 2 beta-18O was incorporated in the formic acid extruded in the aromatization. On this basis we concluded that [5a] can not be an obligatory precursor of estrogen biosynthesis. The trapping of radioactive androst-4-ene-2 beta,3 beta,17 beta,19-tetrol in a reductively terminated incubation of a mixture of radioactive androst-4-ene-3,17-dione and [5a] with crude placental aromatase was interpreted as evidence in support of the intermediacy of [5a]. We confirmed that the tetrol can indeed be trapped in the reductively terminated incubations. However, considering that the crude placental enzyme preparation very likely contains numerous activated oxygen species capable of a variety of oxidation reactions, most of which may not be related to estrogen elaboration, and in view of our results quoted above, the origin and the eventual biosynthetic role of the parent compound of the tetrol remains to be determined.
Steroids
PMID:Concerning the pathway from 19-oxoandrost-4-ene-3,17-dione to estrone. 350 12

Rapid and accurate assay methods for cholesterol:NADPH oxidoreductase (EC 1.14.13.17, 7 alpha-hydroxylating) and 7 alpha-hydroxy-4-cholesten-3-one 12 alpha-hydroxylase (enzyme not yet registered) are described. 7 alpha-Hydroxylase utilizes the endogenous cholesterol of liver microsomes as substrate. The reaction products were separated by high performance liquid chromatography monitored at 214 nm. Much higher activity was obtained with the method compared to literature values, which were obtained using externally added radioactive cholesterol as the substrate. The 12 alpha-hydroxylase activity was measured using non-radioactive steroid as the substrate. The reaction products were separated by the chromatography and detected at 240 nm. Comparable activities were obtained by this method compared to those that were obtained using radioactive substrate.
Steroids 1985 Jun
PMID:Assays for cholesterol 7 alpha-hydroxylase and 12 alpha-hydroxylase using high performance liquid chromatography. 393 46

A number of diverse biological compounds involved in the regulation of the hypothalamo-hypophyseal-ovarian axis have been examined for effects on the conversion of 3H-progesterone to 3H-5 alpha-dihydro-progesterone and 3H-3 alpha-hydroxy-5 alpha-pregnan-20-one by female rat hypothalamus and/or anterior pituitary. Broken cell preparations were incubated with 3H-progesterone and NADPH, and product 5 alpha-reduced progestins were quantitated by reverse isotopic dilution analysis. Progesterone 5 alpha-reductase activity was reduced up to 50% in the presence of 10(-2) to 10(-3) M serotonin in both preparations. At 10(-3) M, various indoles including n-acetylserotonin, melatonin, 5-methoxytryptamine, 5-methoxytryptophol, and 5-hydroxyindole acetic acid decreased by 10 to 30% 5 alpha-reduced product formation. At 10(-2) M, carbamylcholine and norepinephrine were without effect, while 10(-2) M dopamine reduced by 20% the 5 alpha-reduction of progesterone only in pituitary homogenates. The LHRH protease inhibitor bacitracin (2 X 10(-3) M) decreased by 10 to 40% progesterone 5 alpha-reductase activity in both tissues. By itself, LHRH did not affect the 5 alpha-reduction of progesterone nor did it potentiate the bacitracin effect. In the presence of 1 mM ATP, 100 micronM cAMP and 100 micronM cGMP increased 5 alpha-reduced product formation in the hypothalamus by 19 and 14%. The gonadotropins LH and FSH and the prostaglandins E1, E2, F1 alpha, and F2 alpha were without effect. Thus, these results and others indicate that a number of cellular components and other factors can affect the in vitro 5 alpha-reduction of progesterone in broken cell preparations.
Steroids 1980 Sep
PMID:The effects of neurotransmitters and other cellular modulators and factors on hypothalamic and anterior pituitary delta 4-steroid (progesterone) 5 alpha-reductase activity. 610 99


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