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)

Preparation of the synthetically useful steroid intermediate 19-d3-androst-4-ene-3,17-dione (Ia) together with its 19-d2-(Ib) and 19-d1-(Ic) analogues is described. The conditions and work-up of the synthesis have been designed to eliminate tedious chromatographic separation and purification steps thus enabling decigrams of material to be conveniently prepared using standard laboratory apparatus. The deuterium label in the C-19 angular methyl group is inert to normal chemical exchange processes, thus offering the opportunity for synthesis of more complex, biologically active, stable labelled steroids, whose metabolism can be studied mass spectrometrically.
Steroids 1979 Jun
PMID:Synthesis of C-19 deuterium labelled steroids. 46 2

3H-Testosterone (3H-T) plus 14C-androst-4-ene-3,17-dione (A-dione) and 3H-epi-testosterone (17alpha-hydroxy-4-androsten-3-one) (epiT) plus 14C-T were injected intravenously into two male sheep with bile fistulae, respectively. Urine and bile samples were collected at intervals for 4-8 hours and analyzed by the use of DEAE-Sephadex A-25 and Lipidex 5000 columns, TLC, and paper chromatography; the aglycones were identified by co-crystallization with authentic standards. Five fractions were obtained from urine and bile: unconjugated, glucosiduronates, sulfates, sulfo-glucosiduronates and disulfates. In urine, the major conjugates were glucosiduronates, while sulfates predominated in bile. About 80-90% of recovered radioactivity was found to be either glucosiduronates or sulfates. Among the metabolites identified, epi-T was the principal one, accounting for 10-15% of the administered doses. Conversion to 17alpha-hydroxysteroids thus appears to be a major route of metabolism of the androgens administered in sheep. Other metabolites in the glucosiduronate and sulfate fractions were androsterone, etiocholanolone (3alpha-hydroxy-5beta-androstan-17-one), 5beta-androstane-3alpha,17beta-diol, two unknown diols and polar metabolites. The results indicated that androgen metabolism is somewhat unusual in sheep, as compared with other animals and the human.
Steroids 1978 Oct
PMID:Androgen metabolism in sheep. 71 26

Steroids inhibit the exchange transport of glucose in human erythrocytes. The extent of inhibition is roughly correlated to the affinity of the steroids to the membrane lipids. All C-21-steroids tested show a competitive inhibition while the C-19-steriods show different types of inhibition. 5Beta-androstane-3,17-dione acts as a competitive inhibitor. The inhibition by testosterone is of mixed type, while with androst-4-ene-3,17-dione and 5alpha-androstane-3,17-dione a non-competitive inhibition is observed. In this case two inhibitor molecules can be bound per transport molecule. The "non-competitive" inhibitors compete also to some extent with the glucose binding. This effect, however, is at high inhibitor concentrations masked by the more powerful non-competitive inhibition. Competitive and non-competitive inhibitors compete with each other. The structural requirements for the different types of inhibition are discussed.
 ...
PMID:Interaction of steroids with the transport system of glucose in human erythrocytes. 120 39

The microorganism Mucor piriformis transforms androst-4-ene-3,17-dione into a major and several minor metabolites. X-ray crystallographic analysis of two of these metabolites was undertaken to determine unambiguously their composition and chirality. Crystals belong to the orthorhombic space-group P2(1)2(1)2(1), with a = 7.199(4) A and a = 6.023(3) A, b = 11.719(3) A and b = 13.455(4) A, c = 20.409(3) A and c = 20.702(4) A for the two title compounds, respectively. The structures have been refined to final R values of 0.060 and 0.040, respectively.
Steroids 1991 Aug
PMID:The identification of 14 alpha,17 beta-dihydroxyandrost-4-en-3-one monohydrate and 14 alpha,17 beta-dihydroxyandrosta-1,4-dien-3-one monohydrate, metabolites of androstenedione in Mucor piriformis. 184 12

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

Sertoli cells isolated from 17 day old rats were maintained in culture and incubated with [14C]-progesterone for 20 h. The cells and media were extracted with ether/chloroform and the extracts chromatographed two-dimensionally on TLC and the radioactive metabolites visualized by autoradiography. Nine of the metabolites (constituting about 88% of total metabolite radioactivity) were identified by relative mobilities of the compounds and their derivatives in TLC and GC systems and by recrystallizations with authentic steroids as the following: 20 alpha-hydroxypregn-4-en-3-one, 3 alpha-hydroxy-5 alpha-pregnan-20-one, 5 alpha-pregnane-3 alpha, 20 alpha-diol, 17 beta-hydroxy-5 alpha-androstan-3-one, 5 alpha-pregnane-3,20-dione, 17-hydroxypregn-4-ene-3,20-dione, testosterone, 5 alpha-androstane-3 alpha, 17 beta-diol and androst-4-ene-3,17-dione. Over 71% of the metabolite radioactivity was due to 20 alpha-hydroxypregn-4-en-3-one, the major metabolite. 5 alpha-reduced pregnanes constituted about 12% and C19 steroids comprised about 2.9% of the radioactivity of the metabolites. Calculation of relative steroidogenic enzyme activities from initial reaction rates suggested the following activities in muunits/mg Sertoli cell protein: 20 alpha-hydroxysteroid oxidoreductase (20 alpha-HSO; 7.71), 5 alpha-reductase (4.77), 3 alpha-HASO (3.57), 17 alpha-hydroxylase (0.93), 17 beta-HSO (0.34) and C17-C20 lyase (0.34). The relatively high rate of steroidogenic enzyme activities in the Sertoli cells of young rats may indicate that Sertoli cells are less dependent on Leydig cell steroidogenesis than has been assumed. Since nearly all the metabolites of progesterone and testosterone are now identified, it is possible to construct a picture of Sertoli cell steroidogenic activity.
Steroids 1980 May
PMID:An analysis of the metabolites of progesterone produced by isolated Sertoli cells at the onset of gametogenesis. 699 80

The cytosol of the filamentous fungus Cochliobolus lunatus was found to contain binding proteins for testosterone and androst-4-ene-3,17-dione. Both of these steroids were also found to be good exogenous substrates for the constitutive 17 beta-hydroxysteroid dehydrogenase, also found in this fungus. We were looking for the possible endogenous substrate. The procedures for isolation and identification of the endogenous steroid molecules in the fungus C. lunatus are described in this paper. The lipids were extracted from the cells and from the growth medium and purified by column and thin-layer chromatography. Analysis of the steroids, isolated from the cells of C. lunatus by gas chromatography and combination of gas chromatography-mass spectrometry, revealed the presence of testosterone and androst-4-ene-3,17-dione. Their structures were confirmed by comparison with the standards on the basis of chromatographic behavior and mass spectra. No such structures were found in the growth medium. Endogenous synthesis of androgens in this fungus was independently confirmed by the detection of radioactively labeled testosterone when the growing cells of C. lunatus were labeled with radioactive precursor molecule [5-3H] mevalonate.
Steroids 1994 Jun
PMID:Isolation and identification of testosterone and androstenedione in the fungus Cochliobolus lunatus. 794 Jun 13

Diastereomeric (19S)- and (19R)-19-ethynyl-19-acetoxy derivatives of androst-4-ene-3,6,17-trione (AT) (9 and 10) and 19,19-difluoro AT (12) were synthesized. The 19,19-difluoro compound (12) was an effective competitive inhibitor of human placental aromatase with an inhibition constant (ki) of 1.8 microM but the acetylenic 9 and 10 were poor inhibitors of the enzyme with k(is) of 75 and 67 microM, respectively. Inhibitor 12 caused a time-dependent, biphasic loss of aromatase activity in the presence of reduced nicotinamide-adenine-dinucleotide phosphate (NADPH) in air, whereas the other two caused a time-dependent, pseudo-first-order inactivation of the activity with rate constants for inactivation of 0.250, 0.077, and 0.065 min-1 for steroids 12, 9, and 10. NADPH was required for the time-dependent inactivation, and the substrate androst-4-ene-3,17-dione prevented it. L-Cysteine did not protect aromatase from the inactivation.
Steroids 1993 Jan
PMID:A time-dependent inactivation of aromatase by 19-substituted androst-4-ene-3,6,17-triones. 843 Apr 44

We describe the synthesis of 13 beta- and 13 alpha-H-18-nor-androst-4-ene-3,17-dione (1a and 1b) from 18-hydroxyprogesterone (18-->20) hemiketal, via the 18-acetoxy-17 beta-hydroxyandrost-4-en-3-one formed by a modified Baeyer-Villiger reaction. Saponification of 18-acetoxyandrost-4-ene-3,17-dione with sonication, then retroaldolization in the presence of a formaldehyde trap, methone, afforded the mixture of 1a and 1b with 80% yield in a "one-pot" procedure and at room temperature. This yield was greatly improved, compared with the already published procedure.
Steroids 1993 Mar
PMID:An improved synthesis of 18-norandrost-4-ene-3,17-dione. 847 19

The regioselective and stereoselective hydroxylation of steroids by fungal strains previously known for their hydroxylation capabilities, such as Thamnostylum (= Helicostylum) piriforme ATCC 8992, Mucor griseocyanus ATCC 1207a, Actinomucor elegans (= Mucor parasiticus) MMP 3122 (Mucorales), and Zygodesmus sp. ATCC 14716, was investigated with special interest for the 14 alpha-hydroxylation reaction. A preliminary screening had shown that some of these microorganisms were adequate for the production of 14 alpha-hydroxylated derivatives of the following steroids: progesterone, 5 beta-pregnane-3,20-dione, 3 beta-hydroxy-5 beta-pregnane-20-one, 3 beta-hydroxy-5 beta-17 (alpha H)-etianic acid methyl ester, androst-4-ene-3,17-dione, and testosterone. About 20 metabolites have been isolated and purified by silicagel chromatography and semi-preparative reverse-phase HPLC. These metabolites have been fully characterized by 1H, 13C NMR and mass spectrometry. All the identified metabolites were hydroxylated at some distinct positions, such as 6 beta-, 7 alpha-, 9 alpha-, 14 alpha-, 15 beta-, or dihydroxylated at 6 beta,14 alpha-,7 alpha,14 alpha-, 9 alpha,14 alpha-, 14 alpha,15 alpha-, 14 alpha,15 beta-positions; nine of these metabolites have not been reported previously. The relationship between the structural features of the investigated steroids and the site-specific hydroxylation has been delineated, and progesterone was found to be the best substrate for the production of 14 alpha-hydroxylated derivative, using T. piriforme.
Steroids 1995 Apr
PMID:Microbial transformation of steroids: contribution to 14 alpha-hydroxylations. 853 88


1 2 3 Next >>