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)

Using unlabeled androsterone as starting material, 5 alpha-[16,16-2H2]androstan-3 alpha-ol-17-one was synthesized by exchange using deuterated potassium methoxide. This labeled androsterone product was reduced by sodium borodeuteride, which gave predominantly trideuterated 5 alpha-androstane-3 alpha, 17 beta-diol. The labeled androstanediol was conjugated with glucuronide by using the Koenig-Knorr reaction with methyl-1-bromo-1-deoxy-2,3,4-tri-O-acetyl-alpha-D-glucopyranosuronate . The dominant product was identified by thermospray high-performance liquid chromatography/mass spectrometry (MS) and electrospray MS as 5 alpha-[16,16,17-2H3]androstane-3 alpha, 17 beta-diol, 17 beta-glucuronide.
Steroids 1992 Nov
PMID:Synthesis of deuterium-labeled 5 alpha-androstane-3 alpha, 17 beta-diol and its 17 beta-glucuronide. 144 12

The 20 alpha-reduced derivative of aldosterone, 20 alpha-dihydroaldosterone, was needed as reference compound in order to continue the studies on 18-hydroxylation in the Y-1 adrenal cell line. It was obtained by reduction of aldosterone with sodium borohydride. Analysis of the products of the reaction as methoxime trimethylsilyl (MO-TMS) derivatives by gas chromatography (GC) and GC-mass spectrometry (GC-MS) showed three possible forms of the compound. Their identification was confirmed by comparison with the products obtained by stereospecific reduction of aldosterone using 3 alpha,20 beta-hydroxysteroid dehydrogenase. Chromatographic behavior and mass spectra are given for the three forms of 20 alpha-dihydroaldosterone as the MO-TMS derivatives; that is, the 18-aldehyde, the 18,11 beta-hemiacetal, and the 11 beta:18,18:20 alpha-acetal. The possible origin of these different forms is discussed as a function of these results and of the results obtained by complementary analysis on high-performance liquid chromatography.
Steroids 1992 Oct
PMID:Chromatographic and mass spectrometric characteristics of 20-dihydroaldosterone. 145 55

Though our understanding of asthma has improved, its incidence, prevalence and associated death rate have been increasing in most industrialized countries. Inadequate treatment of airway inflammation may explain some of this trend. Steroids are the most effective anti-inflammatory agents and are effective and safe in inhaled form. Together with sodium cromolyn, they should be used more frequently in the management of all types of asthmatics, especially those who require chronic or acute administration of oral steroids.
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PMID:Selections from current literature: inhaled steroid use in asthma management. 149 May 48

Synthesis of 25R- and 25S-diastereoisomers of 3 alpha,7 alpha-dihydroxy-5 beta-cholestan-26-oic acid from 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid is described. The 25S-diastereoisomer of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan- 26-oic acid was obtained by vigorous hydrolysis of the bile of Alligator mississippiensis followed by repeated crystallization of the hydrolysate, and the 25R-diastereoisomer was isolated by hydrolysis of the bile salts in bile of A mississippiensis with rat feces. Acetylation of the 25R- or 25S-diastereoisomer of methyl 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid under controlled conditions yielded the corresponding 3 alpha,7 alpha-diacetate in approximately 70% yield. The diacetate was quantitatively oxidized to methyl 3 alpha,7 alpha-diacetoxy-12-oxo-5 beta-cholestan-26-oate, which was converted into the 12-tosylhydrazone in approximately 58% yield. Reduction of the tosylhydrazone with sodium borohydride in acetic acid yielded the 25R- or the 25S-diastereoisomer of 3 alpha,7 alpha-dihydroxy-5 beta-cholestan-26-oic acid as the major product. Purification via column chromatography yielded the pure diastereoisomers in approximately 25% overall yield. The two diastereoisomers were resolved on thin-layer chromatography and high-performance liquid chromatography. When the bile of A mississippiensis was hydrolyzed with rat fecal bacteria, the 3 alpha,7 alpha-dihydroxy-5 beta-cholestan-26-oic acid isolated via chromatographic purification was shown to be the 25R-diastereoisomer.
Steroids 1992 Apr
PMID:Synthesis of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestan-26-oic acid from 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid: configuration in the bile of Alligator mississippiensis. 151 59

Steroids (aldosterone and testosterone) and peptides of cerebral origin (angiotensin II and the tachykinins) control the salt intake of the rat. They arouse or suppress the behaviour and produce life-long enhancements of NaCl intake. Need-induced salt intake (salt appetite or salt hunger), which is the consequence of sodium deficiency, is aroused by a synergy within the brain of cerebral angiotensin II and aldosterone. And prior episodes of sodium depletion produce enhancements of subsequent salt appetites, but only if the prior depletions were accompanied by angiotensin II and aldosterone action. Need-free salt intake, which occurs daily when the rat is in positive sodium balance, is inherently high in the rat and is organized in the perinatal period by aromatized testosterone which suppresses the intake of the male. It is also enhanced by prior activations of angiotensin II and aldosterone. Both need-induced and need-free salt intake are suppressed by intracranial tachykinins. Non-mammalian tachykinins (eledoisin, physalaemin, kassinin) are both antidipsogenic and antinatriorexigenic, but amino-senktide, an analogue of the mammalian tachykinin substance P with selective affinity for the NK 3 receptor, appears to be a selective antinatriorexigenic agent, and could provide a rational therapy for chronic overconsumption of salt.
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PMID:Control of salt intake by steroids and cerebral peptides. 163 90

19-Nordeoxycorticosterone (19-nor-DOC) is a mineralocorticoid with several unresolved physiologic questions. First, is 19-nor-DOC synthesized in the kidney from a circulating adrenocortical precursor (19-oicdeoxycorticosterone [19-oic-DOC] or 19-oxodeoxycorticosterone [19-oxo-DOC])? Second, does 19-nor-DOC, synthesized in the kidney, have mineralocorticoid activity or is it excreted in the urine without biologic activity? To answer this question, we administered two of the putative 19-nor-DOC precursors (19-oxo-DOC and 19-oic-DOC) to adrenalectomized rats and measured the formation of 19-nor-DOC and bioactivity as the urinary Na+ to K+ ratio. Each of the 10-microgram steroid treatments produced an elevation of urinary-free 19-nor-DOC (0 to 2 hours), whereas at the 1-micrograms dose only 19-oic-DOCA produced an increased UF 19-nor-DOC. None of the treatments led to an increase of conjugated 19-nor-DOC except 10 microgram 19-oic-DOCA. Increased mineralocorticoid activity (decreased urinary Na+ to K+ ratio) was produced by aldosterone, 1 and 10 micrograms 19-nor-DOC, and 10 micrograms 19-oic-DOCA over the same time period. An anti-mineralocorticoid effect (increased urinary Na+ to K+ ratio) was produced by 1 microgram 19-oxo-DOC. Urinary-free 19-nor-DOC, but not conjugated 19-nor-DOC, correlated with the urinary mineralocorticoid effect (decreased Na+ to K+ ratio). These data support the contention that 19-oic-DOC is the circulating 19-nor-DOC precursor and that, at least at the higher dose, it has a mineralocorticoid action on the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1991 Nov
PMID:Comparison of the mineralocorticoid activity of 19-oxygenated and 19-nor derivatives of deoxycorticosterone. 181 21

Liver cytochrome P450 monooxygenases (P450), a group of isozymes that catalyze the reductive cleavage of molecular oxygen, dominate hepatic metabolism of xenobiotic lipophilic substances. These P450 enzymes exhibit broad and overlapping substrate specificities, in contrast to the P450 isozymes of the steroid biosynthetic pathways, which are highly substrate specific. Hepatic heme pigments, N-alkylated porphyrins, accumulate following the self-catalyzed destruction of P450 by the metabolic activation of 17 alpha-ethynyl steroids. Acetylenic substituted steroidal aromatase inactivators, norethisterone (NET), and 10-(2-propynyl)estr-4-ene-3,17-dione (MDL 18,962) were administered to rats to determine if the acetylenic substituent was activated by hepatic P450 mixed-function oxidases. This metabolism could result in the formation of a reactive species that would alkylate a pyrrole nitrogen atom of heme. Male Sprague-Dawley rats were treated with 0, 10, 30, or 100 mg/kg NET or MDL 18,962 intraperitoneally. Four hours later, these animals received 40 mg/kg sodium pentobarbital and their sleeping times were recorded. On arousal, the rats were killed and their livers were taken for determination of P450 content and formation of N-alkylated porphyrins (green pigments). Norethisterone inhibited hepatic P450 isozymes, resulting in a dose-related increased sleeping time (89.2 +/- 3.5 to 156.3 +/- 7.6 minutes) and decreased P450 levels (maximum 25% decrease at 100 mg/kg), and the amount of green pigments increased with doses of 10 to 100 mg/kg. In contrast, MDL 18,962 treatment did not increase sleeping time and caused only a 15% decrease in hepatic P450 content at 100 mg/kg, with no detectable green pigments.(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1991 Apr
PMID:Regioselectivity of metabolic activation of acetylenic steroids by hepatic cytochrome P450 isozymes. 187 82

A few pregnane derivatives were synthesized from 1,2-dehydroprogesterone (1). Ring A of 1,2-dehydroprogesterone was aromatized without affecting C-20, and the resulting acetoxy compound (2) after hydrolysis yielded 1-hydroxy-4-methyl-19-norpregna-1,3,5(10)-trien-20-one (3). Reactions of the phenol (3) with alkyl halides yielded the ethers 6a-6b and 7. Opening of the oxirane ring in 7 with secondary amines furnished the aminoalcohols 8a-8b. Friedelcraft's reaction of 3 with maleic anhydride and chloracetyl chloride led to the formation of 9 and 10, respectively. Base-catalyzed ring closure of 10 yielded 1-acetyl-12a-methyl-8-oxo-5[H]-1,2,3,3a,3b,4,8,9,10b,11,12, 12a-dodecahydrocyclopenta (7,8)-phenanthro (3,4-b) furan (11), which reacted with aromatic aldehydes regioselectively to furnish 12a-12b. Reaction of 1 with triethylorthoformate in the presence of boron trifluoride etherate involved the participation of C-21, and the carbonyl at C-3 remained unaffected. The product 13 was identified as 21-[2-hydroxyvinyl]-21-norpregna-1,4-diene-3,20-dione. Reductive amination with sodium cyanoborohydride in the presence of ammonium acetate did not attack ring A and smoothly furnished the amine 14 which, on reaction with succinic anhydride, gave 20-succinamylpregna-1,4-dien-3-one (15).
Steroids 1991 Apr
PMID:Regioselective reactions of 1,2-dehydroprogesterone: syntheses of pregnane derivatives as possible contragestational agents. 187 84

A commercially available antidihydrotestosterone antiserum was used for the direct radioimmunoassay of androstenediol-3-sulfate (ADS) in human serum. Aliquots of 1 or 2 microliter male serum (mean age of 40 subjects, 38.2 +/- 5.0 years) were diluted and extracted with ethanol for assay. The tracer, [7-3H]ADS, was prepared by sodium borohydride reduction of [7-3H]dehydroepiandrosterone sulfate (DS). Significantly cross-reacting steroids were testosterone, DS, androsterone sulfate, and epiandrosterone sulfate, which combined to produce a mean overestimation of ADS of 4.3 micrograms/dl in male serum. Mean serum ADS was 23.6 +/- 10.0 micrograms/dl (SD) in 20 fresh-frozen sera versus 28.4 +/- 9.7 micrograms/dl (SD) in 20 long-term (24.4 +/- 1.2 years) frozen specimens, showing stability on long-term frozen storage. Androstenediol-3-sulfate also showed a strong correlation with serum DS (r = 0.75). The possible physiologic significance of ADS is discussed, particularly in terms of the known estrogenicity of unconjugated androstenediol.
Steroids 1991 Jun
PMID:Direct radioimmunoassay of androstenediol-3-sulfate in the serum of normal men. 192 28

Steroids (aldosterone and testosterone) and peptides of cerebral origin (angiotensin II and the tachykinins) control the salt intake of the rat. They arouse or suppress the behavior and they produce lifelong enhancements of NaCl intake. Need-induced salt intake (salt appetite or salt hunger), which is the consequence of sodium deficiency, is aroused by a synergy within the brain of cerebral angiotensin II and aldosterone. And prior episodes of sodium depletion produce enhancements of subsequent salt appetites, but only if the prior depletions were accompanied by angiotensin II and aldosterone action. Need-free salt intake, which occurs daily when the rat is in positive sodium balance is also enhanced by prior activations of angiotensin II and aldosterone. Both need-induced and need-free salt intake are suppressed by intracranial tachykinins. Nonmammalian tachykinins (eledoisin, physalaemin, kassinin) are both antidipsogenic and antinatriorexigenic, but amino-senktide, an analog of the mammalian tachykinin substance P with selective affinity for the NK 3 receptor, appears to be a selective antinatriorexigenic agent, and could provide a rational therapy for chronic over-consumption of salt.
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PMID:Neurohormonal control of salt intake in the rat. 195 25


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