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

The proportion of 20 alpha/20 beta-epimers of the urinary C21-steroid metabolites was estimated in normal volunteers and in patients with congenital adrenal hyperplasia (CAH), postpubertal virilizing syndrome (PVS) and polycystic ovary syndrome (POS). In the normal individuals 20 alpha- and 20 beta-epimers of 5 beta-pregnane-3 alpha, 17 alpha, 20-triol (pregnanetriol) and 5-pregnene-3 beta, 17 alpha, 20-triol (5-pregnenetriol) were measured. In the other case 20 alpha- and 20 beta-epimers of the characteristic, representative metabolites were also investigated. In 26 of 27 normal persons and in all the patients with normotensive CAH, PVS and POS the 20 beta-epimer comprised 0-10% of the total pregnanetriol. The 20 beta-epimer of 5-pregnenetriol was found in only one normal case (6% of the total). The percentage of 20 beta-epimers of 3 alpha, 17 alpha, 20-trihydroxy-5 beta-pregnan-11-one, 5 beta-pregnane-3 alpha, 11 beta, 17 alpha, 20-tetrol (in the normotensive CAH, PVS and POS) and 5 alpha- or 5 beta-pregnane-3 alpha, 17 alpha, 20, 21-tetrol (in the hypertensive CAH) varied from nil to 76%. The effect of functional groups and the stereochemistry of the molecule on the direction of C-20-keto group reduction is discussed; the existence of additional factors determining this reduction in certain pathological conditions is suggested.
Steroids 1979 Jan
PMID:Isolation of urinary C-20 alpha- and C-20 beta-hydroxy-C21-steroid metabolites in cases of congenital adrenal hyperplasia, postpubertal virilizing syndrome and polycystic ovary syndrome. 22 14

Synthesis of 3H-pregnanetriolone permitted the estimation of pregnanetriolone in urine with a sensitivity in excess of most previous claims. A good correlation (r = +0.97) was obtained between the values from gas liquid chromatography and those of a double isotope derivative method. In contrast to previous reports, these methods indicated that pregnanetriolone is excreted by normal adults. Urinary pregnanetriolone levels were 18-59 mug/24hr for normal subjects, 35-290mug/24hr in Cushing's syndrome and 250-7000 mug/24hr with congenital adrenal hyperplasia. It is concluded that pregnanetriolone is a normal steroid metabolite and its occurrence in Cushing's syndrome does not necessary indicate an abnormal steroid biosynthetic pathway.
Steroids 1976 Feb
PMID:Pregnanetriolone, a normal steroid metabolite: its excretion by normal, Cushing's syndrome and congenital adrenal hyperplasia subjects. 127 87

A method is reported for the measurement of the urine excretion rates of tetrahydro-11-deoxycorticosterone (3 alpha,5 beta-THDOC), an important metabolite of 11-deoxycorticosterone (DOC). Quantification using gas chromatography/mass spectrometry (GC/MS) was achieved by comparing the ion fragment response for the molecular ion (m/z 507) of the analyte (as methyloxime trimethylsilyl ether derivative) to that of a fixed amount of an isomer of THDOC added to urine as internal standard. To improve the specificity of measuring THDOC in clinical samples, an additional Sephadex LH-20 chromatography step was introduced to separate 11-deoxycortisol and some progesterone metabolites. In the luteal phase of the menstrual cycle, THDOC excretion was higher than in the follicular phase; it was also higher than in women taking oral contraceptives. The correlation of THDOC with progesterone production, independent of a constant cortisol output, supports an ovarian or peripheral conversion of progesterone to DOC. The assay proved useful (1) in monitoring for the recurrence of a mineralocorticoid-secreting tumor and (2) when adrenal production of DOC was not fully suppressed in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Under the latter circumstances, the renin-angiotensin system seemed to be an important regulator of DOC production.
Steroids 1992 Jan
PMID:Adrenal cortex, tumor, and peripheral production of deoxycorticosterone. 131 48

17-Hydroxyprogesterone is a well-known precursor of androstenedione in adrenal biosynthesis. This study using sheep adrenal incubations demonstrates that 11-deoxycortisol, the precursor of cortisol synthesis, also can be a precursor of androstenedione. Indeed, our data show that androstenedione synthesis is negatively correlated to the synthesis of cortisol and cortisone. This fact allowed us to infer that this new pathway is closely related to the activity of the 11 beta-hydroxylase that is responsible for the synthesis of cortisol. Indeed, when the activity of this enzyme is impaired, 11-deoxycortisol follows the pathway that leads to androstenedione synthesis in the adrenals. This pathway could explain, at least in part, the marked increase of androstenedione observed in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency.
Steroids 1991 Jan
PMID:Evidence for a new biologic pathway of androstenedione synthesis from 11-deoxycortisol. 202 80

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

In 2 sibs pseudohypoaldosteronism was diagnosed by measurements of high serum aldosterone and elevated plasma renin activity. During their first week of life the first born girl, phenotypically normal, went through a severe salt-losing crisis with hyponatremia and hyperkalemia. Steroids given because of suspected congenital adrenal hyperplasia had no effect. High parenteral and later oral substitution of sodium normalized the serum electrolytes. The younger brother had milder symptoms. His salt-losing crisis developing during the first week of life was treated immediately with salt substitution. Both children developed normally with high oral sodium chloride supplementation, as regulated by the parents, using daily body weight measurements. Both children frequently suffer salt-losing crises, generally preceded by simple upper respiratory tract infections, which have to be treated in the hospital by infusion with a hyperosmolar sodium chloride solution.
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PMID:[Pseudohypoaldosteronism--renal salt loss syndrome. Therapy and course exemplified by 2 siblings]. 294 88

21-Hydroxypregnenolone and its metabolite 5-pregnene-3 beta, 20 alpha 21-triol have been measured in the sulfate fraction of neonatal urine. These two steroids are the major two 21-hydroxylated 5-pregnenes produced by neonates and are almost exclusively excreted as disulfates. The excretions of these steroids by normal infants and infants with 21-hydroxylase deficiency were compared. In addition to measurement of the absolute excretion, the excretion relative to the total 3 beta-hydroxy-5-ene output was also determined. The results show that 21-hydroxypregnenolone excretion is highly elevated in 21-hydroxylase deficiency (affected, mean 887 micrograms/24 h, range 453-1431 micrograms/24 h; normal, mean 117 micrograms/24 h, range 17-263 micrograms/24 h), but when compared to excretion of other delta 5 steroids the excretion is slightly low [(21-hydroxypregnenolone + 5-pregnene-3 beta, 20 alpha, 21-triol)/total 3-beta-hydroxy-5-ene steroids, 2.9% affected; 3.6% normal]. This difference was not statistically significant. There is thus no evidence that the 21-hydroxylase acting on pregnenolone is deficient in congenital adrenal hyperplasia. The explanation of the normal activity of "pregnenolone 21-hydroxylase," although not clearly defined, is probably associated with two recent findings by other workers: (a) that the human fetus has an active 21-hydroxylase distinct from the adrenal enzyme and (b) that a 21-hydroxylase structurally very different from the adrenal enzyme, with high activity towards pregnenolone (but no activity towards 17-hydroxyprogesterone), has been isolated from rabbit hepatic microsomes.
Steroids
PMID:A paradox: elevated 21-hydroxypregnenolone production in newborns with 21-hydroxylase deficiency. 350 60

A specific radioimmunoassay (RIA) method is described for the determination of 21-deoxycorticosterone (21 DB) in human plasma. 21-Deoxycorticosterone-3-(O-carboxymethyl) oxime-bovine serum albumin conjugate was used to generate antisera in rabbits. Steroids which reacted significantly with the antisera were found to be progesterone, pregnenolone, corticosterone and 11-oxo progesterone. However, after extraction of plasma and column chromatography on Celite, all these steroids were separated from 21-deoxycorticosterone and consequently did not interfere with the radioimmunoassay. The intra- and interassays coefficients of variation were 8% and 11% respectively. Mean plasma 21-deoxycorticosterone level for healthy subjects was very low: 17.8 +/- 14.8 pmol/l (mean +/- SD) with no statistical difference between males and females. During the ACTH stimulation test, the 21-deoxycorticosterone levels of healthy subjects increased to 84.7 +/- 26.3 pmol/l (mean +/- SD) for males and 79.3 +/- 31.6 pmol/l (mean +/- SD) for females. Consequently high levels of plasma 21-deoxycorticosterone were found in treated patients suffering from congenital adrenal hyperplasia (CAH) with 21-hydroxylase deficiency, particularly in CAH salt-losers with high plasma renin activity (PRA), where the plasma level reached 40,545 pmol/l. Thus, 21-deoxycorticosterone may be a new marker for adrenal 21-hydroxylase deficiency.
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PMID:The measurement of 11 beta-hydroxy-4-pregnene-3,20-dione (21-deoxycorticosterone) by radioimmunoassay in human plasma. 354 44

In recent years several 15 beta-hydroxysteroids have emerged pathognomonic of adrenal disorders in human neonates of which 3 alpha,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (2) was the first to be identified in the urine of newborn infants affected with congenital adrenal hyperplasia. In this investigation we report the synthesis of the three remaining 3 xi,5 xi-isomers, namely 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (3), 3 beta,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one (7) and 3 beta,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (8) for their definitive identification in pathological conditions in human neonates. 3 beta,15 beta-Diacetoxy-17 alpha-hydroxy-5-pregnen-20-one (11), a product of chemical synthesis was converted to the isomeric 3 and 7, while conversion of 15 beta,17 alpha-dihydroxy-4-pregnen-3,20-dione (4), a product of microbiological transformation, resulted in the preparation of 8. In brief, selective acetate hydrolysis of 11 gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5-pregnen-20-one (12) which on catalytic hydrogenation gave 15 beta-acetoxy-3 beta,17 alpha-dihydroxy-5 alpha-pregnan-20-one (13) a common intermediate for the synthesis of the 3 beta(and alpha),5 alpha-isomers. Hydrolysis of the 15 beta-acetate gave 7, whereas oxidation with pyridinium chlorochromate gave 15 beta-acetoxy-17 alpha-hydroxy-5 alpha-pregnan-3,20-dione (14) which on reduction with L-Selectride and hydrolysis of the 15 beta-acetate gave 3. Finally, hydrogenation of 4 gave 15 beta, 17 alpha-dihydroxy-5 beta-pregnan-3,20-dione (10) which on reduction with L-Selectride gave 8.
Steroids 1995 Dec
PMID:15 beta-hydroxysteroids (Part IV). Steroids of the human perinatal period: the synthesis of 3 alpha,15 beta,17 alpha-trihydroxy-5 alpha-pregnan-20-one and its A/B-ring configurational isomers. 865 Jul 1

Steroids hydroxylated at C-15 have long provided useful information about the well-being of the fetus and feto-placental unit in human pregnancy. In an attempt to develop a new and reliable immunoassay method for use in newborn screening programs for congenital adrenal hyperplasia, we report the chemical synthesis of 3 alpha,15 beta,17 alpha-trihydroxy-5 beta-pregnan-20-one (2) from 3 alpha-hydroxy-5 beta-androstan-17-one (4) in 9 steps. In brief, 3 alpha-hydroxy-5 beta-androst-15-en-17-one (6), was obtained from 4 by phenylselenation yielding 3 alpha-hydroxy-16 alpha-phenylseleno-5 beta- androstan-17-one (5a) which on dehydroselenation gave 6. Introduction of the 15 beta-hydroxy group and the side-chain was achieved by the addition of 2-lithio-2-methyl-1,3- dithiane followed by an acid-catalyzed rearrangement to give 20,20-trimethylenedithio-5 beta-pregn-16-en- 3 alpha,15 beta-diol (8a). Acetylation then cleavage of the dithioacetal gave 3 alpha,15 beta-diacetoxy-5 beta-pregn-16-en- 20-one (9) which on hydrogenation gave 3 alpha,15 beta-diacetoxy-5 beta-pregnan-20-one (10). Reaction of base and oxygenation of 10 gave a mixture of products which on basic hydrolysis gave 3 alpha,15 beta,17 alpha-trihydroxy-5 beta- pregnan-20-one (2) in an overall yield of 8.8%.
Steroids 1996 Feb
PMID:15 beta-hydroxysteroids (part II). Steroids of the human perinatal period: the synthesis of 3 alpha,15 beta, 17 alpha-trihydroxy-5 beta-pregnan-20-one. 875 Apr 37


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