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Query: UMLS:C0338671 (Steroids)
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Following i.v. administration of [4-14C]cortisol, various sulfate conjugated metabolites of cortisol in urine were identified and their respective excretion rates measured. The results obtained demonstrated the following: 1) sulfate conjugates as a group are excreted considerably slower than glucuronide conjugates; 2) sulfate conjugates of steroids with non-reduced ring-A (C-21 sulfates) are excreted (and presumably formed) much faster than steroid-3-sulfates, which require reduction of the ring-A prior to the conjugation; 3) the excretion of C-3 sulfates of ring-A reduced steroids with glycerol side-chain (cortols and cortolones) is significantly faster than those of the corresponding steroids with dihydroxyacetone side-chain (THF, THE and their 5alpha-isomers); 4) the relative concentrations of C-21 sulfates of steroids with ring-A intact (FK, EK, ER, epiER and 6beta-hydroxycortisol) are much higher than the concentrations of C-21 glucuronides of these steroids.
Steroids 1975 Jun
PMID:Studies on steroid conjugates: IX. Urinary excretion of sulfate conjugated metabolites of cortisol in man. 115 50

A urinary method of determining the cortisol production rate (CPR) in children was studied under physiologic conditions by administration of low amounts of [1,2,3,4-13C]cortisol. The CPR in three patients with multiple pituitary deficiency ranged from 7 to 16 mumoles d-1 m-2, and the CPR in three patients with congenital adrenal hyperplasia (CAH) due to 11 beta-hydroxylase deficiency (11 beta OHD) and 17 alpha-hydroxylase deficiency (17 alpha OHD) from 0.1 to 2.11 mumoles d-1 m-2. Results showed that with this method, very low CPRs can be reliably measured. The metabolism of [13C4]cortisol or [9,12,12-2H]cortisol was compared with that of native cortisol in adrenalectomized piglets. For the urinary cortisol metabolites, small to substantial differences in isotope dilution were noted relative to that in the original cortisol mixture. With [13C4]cortisol, the so-called secondary isotope effects were approximately 2% to 3% for tetrahydrocortisone (THE) and tetrahydrocortisol (THF), and about 10% for the cortolones, relative to the cortisol mixture. When [2H3]cortisol was used, the cortisol metabolites THE and THF contained only two deuterium atoms. Together with this apparent loss of one deuterium atom, the secondary isotope effects in these steroids amounted to 5% to 10%. It was concluded that [13C4]cortisol was the better tracer to use for the measurement of urinary CPR.
Steroids 1990 Apr
PMID:Cortisol production rate in children by gas chromatography/mass spectrometry using [1,2,3,4-13C]cortisol. 233 46

During continuous infusion of 3H-cortisol in the circulation of the guinea-pig mother or fetus, radioactive metabolites appear in both maternal and fetal blood. These cortisol-derived compounds were identified principally as cortisone, tetrahydrocortisol (THF) and tetrahydrocortisone (THE). There were unidentified others in low quantities. The cortisone of the maternal plasma is 100% maternal in origin since that of the fetal plasma is 50% fetal in origin between days 62 and 66 and increased thereafter. An identical profile was noted for THF. THE seemed to be synthetized in the fetal guinea-pig and was transferred to the mother in increasing amounts near term. Liver concentrations of cortisol were higher than those of plasma in the mother. Maternal liver appeared to be the main organ of cortisol metabolism in the mother-fetus unit, but maternal adrenal may contribute to this metabolism.
Steroids 1983 Nov
PMID:The conversion of cortisol into its principal metabolites, their tissular concentrations and transplacental transfer during 3H-cortisol infusion of mother and fetal guinea-pigs. 668 Sep 26

The syndrome of apparent mineralocorticoid excess (AME) is a heritable form of hypertension due to an inborn error of cortisol metabolism and is characterized by hypokalemia and low renin levels despite subnormal or normal levels of aldosterone and other known mineralocorticoids. The syndrome is attributable to congenital deficiency of the enzyme 11 beta-hydroxydehydrogenase (11 beta-HSD), which converts cortisol (F) to biologically inactive cortisone. This results in a prolonged half-life of F, which acts at the kidney level as a potent mineralocorticoid (MC). In fact, both F and aldosterone have similar affinities in vitro for type I MC receptor (MR), and 11 beta-HSD activity protects the MR in vivo from the higher circulating levels of F. The biochemical marker of this disorder is an increased ratio of tetrahydrocortisol (THF) + allo-THF/tetrahydrocortisone (THE) in the urine, which has been found in more than 20 patients described to date, together with evidence of a more general defect in steroid ring A reduction. Only a few cases (the so-called type II form) described in Italy differ from the classic form having a normal THF/THE ratio, but in both forms the ratio of free urinary F/E has recently been found to be similarly high. Dexamethasone is the treatment of choice but is often inadequate in long term control of high blood pressure. Acquired forms of AME are those consequent on abuse of licorice or carbenoxolone, which both inhibit 11 beta-HSD; the latter also inhibits the reverse 11-oxoreductase reaction leading to somewhat different abnormalities of urinary cortisol/cortisone. So far, two isoenzymes of 11 beta-HSD have been purified and cloned; 11 beta-HSD type 1 is NADP-dependent, abundant in liver, lung, and testis, and catalyzes both 11 beta-dehydrogenation and 11 beta-oxoreduction; no mutation in its gene was detected in patients with AME. A second NAD-dependent isoenzyme is present in kidney and placenta and catalyzes dehydrogenation only. Very recently (1995) two groups have independently demonstrated the presence of mutations in its gene, located in chromosome 16q22. New and co-workers found a point mutation in exon 6 of two affected siblings of an Iranian family, while White and co-workers in parallel studies showed point mutations or small deletions in both alleles in nine unrelated patients; importantly, expression studies showed minimal or absent activity for almost all the mutant sequences. No definite mutations have been so far identified in patients with AME type II. AME is thus the third single gene cause of human hypertension to be described, after glucocorticoid remediable aldosteronism in 1992 and Liddle's syndrome in 1994.
Steroids 1996 Apr
PMID:Apparent mineralocorticoid excess: type I and type II. 873 99

The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension in which 11 beta-hydroxysteroid dehydrogenase (11-HSD) is defective. This enzyme converts cortisol to its inactive metabolite, cortisone. The deficiency allows mineralocorticoid receptors to be occupied by cortisol, because these receptors themselves have similar affinities for cortisol and aldosterone. There are two isozymes of 11-HSD, a liver (L) or type 1 isozyme with a relatively low affinity for steroids, and a kidney (K) or type 2 isozyme with high steroid affinity. Mutations in the gene for the kidney isozyme of 11-HSD have been detected in all kindreds with AME. We expressed enzymes carrying all known missense mutations in cultured cells and determined their activity. For each patient with AME, we compared the enzymatic activity predicted by the genotype with the ratio of cortisol to cortisone metabolites in the urine, (THF + aTHF)/THE. These were strongly correlated, suggesting that the biochemical phenotype of AME is largely determined by genotype. The K isozyme of 11-HSD is also expressed in high levels in the placenta, where its function is unclear. AME patients often have low birth weight. By analogy with AME, low placental 11-HSD K activity in humans might be a risk factor for low birth weight and subsequent hypertension. However, we found that there was no significant correlation between 11-HSD activity, mRNA levels, and either fetal or placental weight.
Steroids 1997 Jan
PMID:Molecular analysis of 11 beta-hydroxysteroid dehydrogenase and its role in the syndrome of apparent mineralocorticoid excess. 902 20

Alkylation of 3,17 beta-bis(2-trimethylsilyl)ethoxymethyl-1,3,5(10) estratriene-6-one (2) with 5-bromo-1-pentene using NaHMDS in THF afforded 3,17 beta-bis(2-trimethylsilyl)ethoxymethyl-7-alpha-(4'pentenyl)-1,3,5(10) estratriene-6-one (3) in excellent stereoselectivity (> 95% epimeric excess). Functionalization of the side chain in compound 3 was accomplished via ozonolysis, oxidation and esterification to give 5 in 72% yield. The reduction of ester (5) using NaBH4 in MeOH afforded the corresponding 6 alpha-hydroxy compound (6) as a single isomer in 72% yield. The hydroxyl group in 6 was removed by converting to the corresponding xanthate (7) followed by reduction using n-Bu3SnH to afford 8 in good yield. Finally, the SEM protective groups in 8 were removed, after which the ester function was hydrolyzed with LiOH to give 7 alpha-(3'-carboxypropyl)estradiol (10), in 10.6% overall yield from 3.
Steroids 1997 Dec
PMID:A stereoselective synthesis of 7 alpha-(3-carboxypropyl) estradiol from a noncontrolled substance. 943 42

The adrenal gland is involved in the control of urinary sodium excretion mainly via the secretion of the mineralocorticoid aldosterone. Although under certain conditions glucocorticoid seem to be also involved in the regulation of sodium homeostasis, there are contradictory reports on the relationship between cortisol secretion and sodium intake. Given recent findings linking regulation of physiological activity of steroids to the activity of specific enzymatic pathways, we have examined changes in urinary excretion of cortisol and its metabolites in eight healthy volunteers on a low sodium diet. Urinary steroids were measured with specific radioimmunoassays after extraction and chromatography (F and E) or after dilution (THF and THE). Excretion of cortisol (124 +/-41 nmol/day) was significantly lower on Day 2 (86 +/- 27 nmol/day, p < 0.01) and Day 7 (85 +/- 25 nmol/day, p < 0.01) of sodium restriction. On the same samples calculated ratios of THF/F (55 +/- 15; 61 +/- 22; 68 +/- 21) and E/F (2.5 +/- 0.6; 2.8 +/- 1.4; 3.0 +/- 1.3) reflecting the activity of 5 beta-reductase and 11 beta-hydroxysteroid dehydrogenase, respectively, showed significant increases in the former on both Days 2 and 7 and for the latter only on Day 7. This study supports the notion that sodium restriction decreases urinary cortisol excretion and provides evidence that increased activity of 5 beta-reductase and lowered metabolism by 11 beta-HSD are presumably the mechanisms of this decrease.
Steroids
PMID:Effect of sodium restriction on urinary excretion of cortisol and its metabolites in humans. 965 46

A method is described for the preparation of multi-labeled tetrahydrocortisol (3alpha,11beta,17alpha,21-tetrahydroxy-5beta-[1, 2,3,4,5-2H5]pregnan-20-one, THF-d5), allo-tetrahydrocortisol (3alpha,11beta,17alpha,21-tetrahydroxy-5alpha-[1 ,2,3,4,5-2H5]pregnan-20-one, allo-THF-d5), and tetrahydrocortisone (3alpha,17alpha,21-trihydroxy-5beta-[1,2,3,4,5-2H5]pre gnane-11,20-dione, THE-d5) containing five non-exchangeable deuterium atoms in the steroid ring A. Reductive deuteration at C-1, C-2, C-3, C-4, and C-5 of prednisolone or prednisone was performed in CH3COOD with rhodium (5%) on alumina under the deuterium atmosphere. The isotopic purities of the labeled compounds as [2H5]-form were estimated to be 86.17 atom%D for THF-d5, 74.46 atom%D for allo-THF-d5 and 81.90 atom%D for THE-d5, based on the ion intensities in the region of the molecular ion of methoxime-trimethylsilyl (MO-TMS) derivatives measured by GC-MS.
Steroids 1999 Dec
PMID:Synthesis of deuterium-labeled tetrahydrocortisol and tetrahydrocortisone for study of cortisol metabolism in humans. 1057 14

The mitogenic agent that disrupts male and female sexual behavior has been isolated from corncob bedding. The disrupting activity resides in an isomeric mixture of linoleic acid derivatives with a tetrahydrofuran ring and two hydroxyl groups (THF-diols) that include 9, (12)-oxy-10, 13-dihydroxtstearic acid and 10, (13)-oxy-9, 12-dihydroxystearic acid. We examined the effects of exposure of male rats to THF-diols in drinking water on several parameters of male sexual behavior. THF-diols disrupt sexual behavior in male rats by reducing mounting and intromission frequencies. The mount, intromission and ejaculatory latencies are enhanced while the ejaculatory responses are diminished. These findings suggest that the THF-diols modulate hypothalamo-pituitary axis to regulate steroid hormone-dependent male sexual behavior.
Steroids 2005 Oct
PMID:Disruption of male sexual behavior in rats by tetrahydrofurandiols (THF-diols). 1592 21

In order to determine whether or not a 19-hydroxymethyl group of 19-hydroxyandrosta-1,4-diene-3,17-dione (2, 19-hydroxy ADD), an intermediate of aromatase-catalyzed estrone formation from ADD, a suicide substrate of aromatase, is eliminated as formaldehyde, we examine chemical nature of removal of the 19-hydroxymethyl group. 19-acetate 3 and 19-tert-butyldimethylsiloxy compound 4 are known to convert rapidly to estrone with treatment of NaOH or n-Bu4NF. Since compound 2 was unstable and unobtainable under these conditions, compounds 3 and 4 as equivalents to compound 2 were used in this study. The acetate 3 with 5 mol/l HCl in acetone and 10% KOH in MeOH along with the silyl ether 4 with 5 mol/l HCl in acetone and 1 mol/l n-Bu4NF in THF gave formaldehyde and estrone in which a ratio of the aldehyde to estrone was near 1. This result indicates that the 19-hydroxymethyl groups of compound 3 and 4 are eliminated as formaldehyde along with estrone derived from the steroid skeleton under the acid or base treatment. The findings suggest that a single hydroxylation at the 19 carbon of ADD (1) would be, chemically, all that was required for estrone formation.
Steroids 2009 Feb
PMID:Chemical aromatization of 19-hydroxyandrosta-1,4-diene-3,17-dione with acid or alkaline: elimination of the 19-hydroxymethyl group as formaldehyde. 1902 74


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