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At least 163 records · Page 9Linked to original sources
PubMed1980

7 alpha- and 7 beta-carboxymethyl-derivatives of 17-hydroxyprogesterone and 11-deoxycortisol. Synthesis and immunogenic properties.

7 alpha- and 7 beta-carboxymethyl-derivatives of 17-hydroxyprogesterone and 11-deoxycortisol have been synthesized. After coupling to bovine serum albumin, they were used to elicit antibodies in rabbits. No major difference in the steroid specificity of the antisera was observed when either 7 alpha- or 7 beta-epimers were used for immunization. In both cases, highly specific antisera were obtained which may possibly be used to assay human plasma 17-hydroxyprogesterone and 11-deoxycortisol without chromatographic purification.

17-Hydroxycorticosteroids↗
PubMed1980

Potential limitations of recrystallization for the definitive identification of radioactive steroids.

The usefulness of recrystallization in establishing the radiochemical purity of steroids is widely recognized, but the potential limitations of the technique have received little attention. The current study reports the failure of standard recrystallization procedures using methanol/water as the solvent pair to separate contaminating 14C-17-hydroxyprogesterone (17-hydroxy-4-pregnene-3, 20-dione) from 3H- and 14C-labeled 11-deoxycortisol (17,21-dihydroxy-4-pregnene-3,20-dione) despite ten serial crystallizations. The standard criteria of radiochemical purity were met despite gross impurity of the crystals as evidenced by thin layer chromatography. Thus, recrystallization may, under certain conditions, yield misleading results when employed as the only method for identifying radioactive steroids. These observations illustrate the importance of an optimal choice of solvent and crystallization conditions, and emphasize the need for confirmation by derivative formation and chromatography.

17-Hydroxycorticosteroids↗
PubMed1982

Solid phase fluoroimmunoassay for 11-deoxycortisol in serum using 21-amino-17-hydroxyprogesterone.

Solid phase fluoroimmunoassay of serum 11-deoxycortisol (17,21-dihydroxy-4-pregnene-3,20-dione) was established using fluorescein isothiocyanate-labelled 11-deoxycortisol and anti-11-deoxycortisol antibody-conjugated polyacrylamide beads. 21-Amino-17-hydroxyprogesterone (21-amino-17-hydroxy-4-pregnene-3,20-dione) was synthesized as a useful derivative for preparing the fluorescent dye conjugate. Serum 11-deoxycortisol was measured with this assay system after extraction and purification by Sephadex LH-20 column chromatography. The minimal amount of 11-deoxycortisol detected was 40 pg/tube and the measurable range was from 0.04 to 5.0 microgram/dl. Intra- and inter-assay coefficients of variation were 8.3% (n=6) and 9.8% (n=5), respectively. 11-deoxycortisol values determined by the present assay correlated well with those determined by radioimmunoassay. The present assay is particularly suitable for estimating the conditions of the pituitary and adrenocortical functions.

17-Hydroxycorticosteroids↗
PubMed1982

delta 1-11-oxa-11-deoxycortisol: a new antiglucocorticoid with activity in vivo.

A new steroid-like compound, delta 1-11-oxa-11-deoxycortisol, was tested in a one-week growth suppression, thymus suppression and adrenal weight suppression bioassay for possible glucocorticoid antagonist activity in vivo. We hypothesized that this compound would have antiglucocorticoid activity based on previous studies of 11-deoxycortisol and delta 1,9(11)-11-deoxycortisol, which were optimal glucocorticoid antagonists in vivo in adrenalectomized rats, but which lost antiglucocorticoid activity in intact animals, apparently due to adrenal 11 beta-hydroxylation. Thus, delta 1-11-oxa-11-deoxycortisol, a compound which cannot undergo 11 beta-hydroxylation, was synthesized and tested as an antiglucocorticoid. This analog had an affinity for the rat thymus glucocorticoid receptor similar to that of its parent compounds (Ki 0.9-3.1 x 10(-7) M). A dose of 1 mg/rat antagonized the effect of 15 microgram of dexamethasone in the growth suppression assay (p less than 0.05) and in the thymus suppression assay (p less than 0.06), but did not antagonize dexamethasone-induced adrenal weight suppression. delta 1-11-Oxa-11-deoxycortisol did not exhibit glucocorticoid activity in any of the three assays. These data suggest that delta 1-11-oxa-11-deoxycortisol may be a pure competitive antagonist of dexamethasone.

17-Hydroxycorticosteroids↗
PubMed1982

A direct radioimmunoassay for 11-deoxycortisol.

A rapid, sensitive and highly specific radioimmunoassay (RIA) for 11-deoxycortisol has been developed and used for the measurement of serum concentrations. Antisera were raised using 11-deoxycortisol -3-carboxymethyloxime-bovine serum albumin as immunogen and showed minimal cross reaction with related steroids. 11-Deoxycortisol-3-carboxymethyloxime was coupled to 125 I-iodohistamine to produce a labelled antigen of high specific activity (s.a. 680 Ci/mmol). The assay was performed for 1h at room temperature and pH 4. Results were correlated with those after extraction, high pressure liquid chromatography and RIA of serum samples (y= 0.78x + 36.9; r = 0.97, p less than 0.001). The accuracy of the method was satisfactory (y = 1.00x - 0.61; r= 0.95; p less than 0.001). Assay sensitivity was 0.3 nmol/l. 11-Deoxycortisol concentrations in normal subjects at 09.OOh were 26-46 nmol/l (37.2 +/- 5.7; x- +/- 1 S.D.). The assay should facilitate the investigation of patients with possible abnormalities of adrenocortical function.

17-Hydroxycorticosteroids↗
PubMed1983

Asymmetric reduction of steroidal 20-ketones: chemical synthesis of corticosteroid derivatives containing the 20 alpha, 21-diol and 17 alpha, 20 alpha, 21-triol side chains.

A method is presented for the chemical synthesis of corticosteroid derivatives containing the 20 alpha, 21-diol and 17 alpha, 20 alpha, 21-triol side chains. The ketol side chains of cortisol, corticosterone, 11-deoxycortisol, and 11-deoxycorticosterone were reduced at C-20 with sodium borohydride in a two-phase system consisting of aqueous calcium chloride and an organic phase of chloroform or ethyl acetate. Stereoselectivity of reduction was 92% alpha-oriented for cortisol and 79% alpha-oriented for 11-deoxycortisol at -27 degrees. The 20 alpha-form diminished relative to the 20 beta-form with increasing temperature. For the 17-deoxy steroids, reduction to the 20 alpha-form was 23% for 11-deoxycorticosterone and 41% for corticosterone. The 20 alpha/20 beta ratios of 17-deoxy steroids were unchanged between 0 degree and -27 degrees. Calcium ions increased the solubility of corticosteroids in the aqueous phase. We propose that calcium ions affect the stereochemistry of reduction by forming a bidentate complex with the side chains of 17 alpha-hydroxy steroids, fixing them in an orientation favorable to 20 alpha-reduction, and by altering the phase partition of the steroids.

Borohydrides↗
PubMed1986

A competitive enzyme-linked immunosorbent assay for plasma 11-deoxycortisol (17,21-dihydroxy-4-pregnene-3,20-dione).

An enzyme-linked immunosorbent assay (ELISA) for 11-deoxycortisol is described for the first time. 11-Deoxycortisol-thyroglobulin conjugate is adsorbed onto the wells of a 96-well ELISA plate and competes with 11-deoxycortisol in the standards or plasma extract for antibody binding sites. After washing, immobilized primary antibody is probed with peroxidase-labeled goat anti-rabbit IgG. The ELISA plate is further washed and o-phenylenediamine added, color developed and the absorbance read at 492 nm. The ELISA shows good agreement with our existing 11-deoxycortisol radioimmunoassay (RIA) and has similar specificity and performance which allow its use in the routine steroid laboratory for assessing pituitary adrenal function by the metyrapone test.

17-Hydroxycorticosteroids↗
PubMedDate not supplied

Identification of 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one as the major ovarian steroid produced by the teleost Micropogonias undulatus during final oocyte maturation.

This study describes the identification of 17 alpha,20 beta, 21-trihydroxy-4-pregnen-3-one (20 beta-dihydro-11-deoxycortisol, 20 beta-S) as a major steroid product of the ovary of Atlantic croaker (Micropogonias undulatus) incubated in vitro. This is the first report which describes 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one as a major product of teleost steroidogenic tissue. The steroid was identified by a variety of methods, including HPLC, TLC, GC-MS, UV absorbance, and reactions with specific enzymes. Full grown oocytes, prior to final oocyte maturation (FOM), accumulated only small amounts of 20 beta-S. However, a substantial increase in 20 beta-S production occurred at the time of FOM. These results suggest that 20 beta-S is a maturational steroid in this species.

17-Hydroxycorticosteroids↗
PubMed1991

Evidence for a new biologic pathway of androstenedione synthesis from 11-deoxycortisol.

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.

Adrenal Glands↗
PubMed1993

Synthesis and characterization of the 6 alpha- and 6 beta-hydroxylated derivatives of corticosterone, 11-dehydrocorticosterone, and 11-deoxycortisol.

This report describes the synthesis of 6 alpha, 17,21- and 6 beta, 17,21-trihydroxypregn-4-ene-3,20-dione, 6 alpha, 7,21- and 6 beta, 11 beta, 21-trihydroxypregn-4-ene-3,20-dione, and--for the first time--that of 6 alpha, 21- and 6 beta, 21-dihydroxypregn-4-ene-3,11,20-trione. The former four compounds were prepared by 6-hydroxylation of 17,21-trihydroxypregn-4-ene-3,20-dione and 11 beta, 21-dihydroxypregn-4-ene-3,20-dione, respectively. This was achieved by autoxidation or by oxidation with 3-chloroperbenzoic acid, of the 3-methoxy-pregna-3,5-dienes of the latter two steroids. The yield of the 6 beta-hydroxylated steroids, but not of their corresponding 6 alpha-epimers, was higher using autoxidation than the peracid. The two 6-hydroxylated pregnenetriones were prepared from 6 alpha, 21-diacetoxy-11 beta-hydroxypregn-4-ene-3,20-dione and 6 beta, 21-diacetoxy-11 beta-hydroxypregn-4-ene-3,20-dione, respectively, by oxidation with pyridinium chlorochromate. The above-mentioned six steroids were identified and characterized by nuclear magnetic resonance, infrared, ultraviolet, high performance liquid chromatography, gas chromatography, and mass spectrometry.

Chlorobenzoates↗
PubMed1994

Other physiological considerations of protective mechanisms of mineralocorticoid action.

Mineralocorticoid receptors (MR) are protected from the effects of endogenous glucocorticoids (GC) in mineralocorticoid (MC) target tissues such as the kidney and the parotid gland. This protection is thought to be provided by 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD). 11 beta-OHSD metabolizes cortisol (in humans) and corticosterone (B) (in the rat) to cortisone and 11-dehydro-B, their respective inactive dehydro products. We have previously shown that the antinatriuretic actions of the MC deoxycorticosterone (DOC) are amplified in carbenoxolone (CBX) treated adrenalectomized (ADX) rats. CBX is believed to inhibit 11 beta-OHSD activity; DOC, however, is not a substrate for this enzyme. We now report on 11-desoxycortisol (11-desoxy-F) and 2 alpha-methylcortisone, substances which possess no intrinsic antinatriuretic activity, are not metabolized by 11 beta-OHSD and yet cause Na+ retention in CBX-treated ADX rats. Given that none of the above steroids are substrates for 11 beta-OHSD it is unlikely that the inhibition of this enzyme is involved in the unmasking of the Na+ retention observed when these substances are given to CBX-treated animals. These results provide further evidence for an additional protective mechanism, that protects MR from the inappropriate binding of excessive amounts of endogenous MCs.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Radioimmunoassay of three deoxycorticoids in human plasma following HPLC separation.

A radioimmunoassay of three deoxycorticoids, namely 11 beta,17 alpha-dihydroxy-4-pregnene-3,20-dione (21-deoxycortisol), 17 alpha,21-dihydroxy-4-pregnene-3,20-dione (11-deoxycortisol), and 21-hydroxy-4-pregnene-3,20-dione (11-deoxycorticosterone) which are important for differential diagnosis of congenital adrenal disorders, is described and evaluated. Antisera against 3-(O-carboxymethyl)oximes conjugated to bovine serum albumin were raised in rabbits. The radioligands were prepared by radioiodination of previously synthesized homologous tyrosine methyl ester derivatives. Following diethyl ether extraction, the steroids were separated from each other and from cross-reactants by HPLC using a Nucleosil C8 reverse-phase column and a methanol-water mixture (7:5, v/v) as an eluent. Normal levels of analyzed steroids ranged from 0.02 to 0.348, 0.185 to 3.80, and 0.013 to 0.299 nmol/l, for 21-deoxycortisol, 11-deoxycortisol and 11-deoxycorticosterone, respectively. The levels of both deoxycortisols rose significantly after ACTH treatment. Data are given with respect to the concentrations of these steroids in some pathological situations such as 21-hydroxylase and 11 beta-hydroxylase block, hyperaldosteronism, and polycystic ovary syndrome.

Adolescent↗
PubMed1995

The scarlet letter: Reichstein's Substance S. A comparison of the angiostatic properties of 5 alpha-tetrahydro S and 5 beta-tetrahydro S.

5 beta-Tetrahydro-Reichstein's Substance S (3 alpha, 5 beta-THS) from different sources yielded variable bioassay activity in the chick chorio-allantoic membrane assay system. Physical characterization showed impure products. Synthesis of this compound by two different routes yielded active and inactive 3 alpha, 5 beta-THS. Of the other two epimers, 3 beta, 5 beta-THS (epi-THS) and 3 alpha, 5 alpha-THS (allo-THS), only the latter was active. These results suggest that the impurities present in 3 alpha, 5 beta-THS synthesized by reduction of the alpha, beta-unsaturated ketone of Substance S might be either or both the epi-/allo-epimers (3 beta, 5 beta-THS and 3 alpha, 5 alpha-THS, respectively), with only the latter contributing the positive angiostatic activity to the mixture. Of the two synthetically derived compounds, only the latter was shown to maintain the activity, whereas 3 alpha, 5 beta-THS was not antiangiogenic.

Allantois↗
PubMed1984

Low adrenal androgenic-anabolic steroids in women with rheumatoid arthritis (RA): gas-liquid chromatographic studies of RA patients and matched normal control women indicating decreased 11-deoxy-17-ketosteroid excretion.

Using GLC, multiple adrenal corticosteroid urinary metabolites, including androgenic-anabolic, glucocorticoid, pregnanediol, and pregnanetriol, were measured in eight ambulatory female RA patients and eight matched normal control subjects on baseline, ACTH-, and metyrapone-stimulation days under carefully monitored clinical research center protocol. Neither group had been treated previously with any steroid hormones. The 11-deoxy-17-KS metabolites, derived from adrenal androgenic-anabolic steroids, and comprising androsterone, etiocholanolone, and DHA, were significantly lower in RA patients on baseline (P less than .001), ACTH (P less than .005)-, and metyrapone (P less than .02)-stimulation days. To the contrary, the 11-oxy-17-KS metabolites, derived mainly from glucocorticoids, showed some lowered excretion at baseline (P less than .05), but none on ACTH- or metyrapone-stimulation. RA patients had lower tetrahydrocortisone (P less than .001) and tetrahydro-11-deoxycortisol (P less than .01) excretion at baseline, but not during ACTH- or metyrapone-stimulation, than control subjects. Pregnanetriol excretion was lower (P less than .005) in RA patients than control subjects only during ACTH-stimulation. No difference was found between groups in tetrahydrocortisol or pregnanediol excretion on any day studied. Under conditions of oral metyrapone administration (750 mg every four hours for seven doses) each control subject increased their DHA excretion, but no RA patient showed an increase over baseline excretion (P less than .02). Except for 11-deoxy-17-KS, no difference was found in the other metabolites studied during metyrapone stimulation, ie, pregnanediol, pregnanetriol, tetrahydro-11-deoxycortisol, and tetrahydrocortisol. The 24-hour oral metyrapone test provided a greater stimulus to total 11-deoxy-17-KS excretion than an eight-hour intravenous ACTH test in control and particularly RA (P less than .01) subjects even though the DHA excretion decreased in the RA groups. Our findings of lower adrenal androgenic-anabolic metabolite excretion in female RA patients than normal matched control subjects under various conditions and other supportive androgenic hormone and metabolite studies reviewed in the English reports suggest an abnormality of adrenal androgen synthesis or metabolism in RA, whether it be a primary predisposing or secondary factor in disease. The recognized female sex preponderance and age-specific patterns of occurrence of RA are consistent with adrenal androgenic function in adrenarche, adrenopause, and later changes in aging. Metabolite excretion patterns at baseline, ACTH-, and metyrapone- stimulation indicate the greatest relative

17-Hydroxycorticosteroids↗
PubMed1982

Further studies of the effects of inhaled glucocorticoids on pituitary-adrenal function in healthy adults.

We compared the effects of increasing doses of beclomethasone dipropionate (BDP) and fluocortin butylester (FCB) on several indices of pituitary-adrenal function in healthy adult subjects. Significant depression of urinary free cortisol excretion and the response to metyrapone was seen only at the highest dose (1600 mg/day) of BDP. This depression was not reflected by frequent measurement of the serum cortisol concentration. FCB used well in excess of its presumed therapeutic dose range showed no evidence of any effect on pituitary-adrenal function. These results confirm that at high doses BDP causes pituitary adrenal suppression. Differences from studies showing reduced adrenal function in children on BDP doses of 400 to 800 mg/day probably reflect differences in the dose per kilogram of body weight. Since the use of FCB was not accompanied by any adverse side effects or evidence of reduced pituitary-adrenal function, it may be a variable alternative for asthmatics who require high doses of inhaled glucocorticoid.

Administration, Intranasal↗
PubMed1991

Molecular characterization of monoclonal anti-steroid antibodies: primary structures of the variable regions of seven antibodies specific for 17 alpha-hydroxyprogesterone or 11-deoxycortisol and their pH-reactivity profiles.

The variable region nucleotide sequences of seven monoclonal anti-steroid antibodies that are specific for the closely related progesterone derivative, 11-deoxycortisol or 17 alpha-hydroxyprogesterone (17-OHP), have been determined by genomic cloning and DNA-sequencing or by direct mRNA-sequencing. As for their heavy chain variable regions, the nucleotide sequences of the SCET.M8.1 (SCET) and OHP 4B2.2.1 (4B2) antibodies were classified into the VH-9 family, while OHP 7D7.2.3 (7D7), 1E9.3.1 (1E9), 57.G6.1 (57) and 138.H8.1 (138) used VH-3 family genes. OHP 101.B11.1 (101) used a gene of the VH-1 family. For their light chain variable regions, SCET and 57 used VK-28 group genes, while 4B2, 7D7, 1E9, 101 and 138 antibodies used genes of the VK-21 subgroups (21A, 21B or 21C). All of the antibodies used different combinations of genes in the VH families and VK groups or subgroups. This indicates that the antibody response against the steroid hapten, 17-OHP, is fairly polyclonal, and several VH/VL combinations show high affinity for progesterone-related steroids. Although the primary structures of hypervariable loop regions of the mAbs were relatively diverse, generally, hydrophobic and aromatic amino acids were rich in these regions. Moreover, the length of heavy chain CDR3 was constant in all the antibodies investigated in this paper as well as the previously reported anti-progesterone monoclonal antibodies (mAbs). This suggests that the length of VH CDR3 in these mAbs has a considerable influence on the formation of antigen-combining pockets. The pH-reactivity profiles for the anti-17-OHP mAbs indicated that the the steroid-mAb binding was independent of pH between pH 4 and 11 in most of the mAbs. The results suggest that the steroid-mAb interactions are not largely affected by the electrostatic environments near the combining sites of these mAbs. Taken together, these data imply that the shape of hydrophobic depressions in the combining sites is important for the binding of relatively large, hydrophobic and rigid haptens like steroids.

17-alpha-Hydroxyprogesterone↗