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

This study was undertaken to examine the performance of the overnight dexamethasone test, i.e., plasma cortisol level at 8-9 AM following dexamethasone 1 mg by mouth at midnight, in screening for Cushing's syndrome. The participants included 19 patients with Cushing's syndrome (17 with Cushing's disease, 1 with adrenal carcinoma, and 1 with ectopic ACTH syndrome) and 96 patients in whom the possibility of Cushing's syndrome was raised but who did not have the disorder. Utilizing our original very conservative cutoff point of plasma 100 nmol/L (3.62 micrograms/dL) above which Cushing's syndrome was suspected, the sensitivity of the test was 100% but the false positive rate was an unsatisfactory 12.5%. However, the lowest plasma cortisol level achieved following the overnight dexamethasone test in patients with Cushing's syndrome was 259 nmol/L (9.39 micrograms/dL). A plasma cortisol cutoff point of 250 nmol/L (9.06 micrograms/dL) yielded no false negatives and the false positive rate fell to 6.25%. Using a cutoff point of 200 nmol/L (7.24 micrograms/dL) the false positive rate was 7.3%. These performance characteristics of the overnight dexamethasone test compare very favorably with the reported experience of all other screening procedures for Cushing's syndrome including the urinary free cortisol excretion rate and the 48 h dexamethasone test, while the overnight dexamethasone procedure is the simplest for both patients and medical personnel. Since it is possible that some very unusual patients may suppress to plasma cortisol levels lower than that seen in the present study, we now recommend the overnight dexamethasone test using a plasma cortisol cutoff point of 200 nmol/L as the procedure of choice when screening for patients with Cushing's syndrome.
Steroids 1994 May
PMID:The overnight dexamethasone test is the procedure of choice in screening for Cushing's syndrome. 807 41

Elucidation of a role for 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) in modulating ligand access to renal mineralocorticoid receptors, together with identification of expression of the enzyme in most mammalian tissues, has raised the possibility (i) that glucocorticoid metabolism might influence corticosteroid receptor activation in other sites which are relevant to blood pressure control (e.g., vascular smooth muscle), and (ii) that abnormal 11 beta-OHSD expression might play a pathogenic role in common forms of hypertension (e.g., essential hypertension and the syndrome of ectopic ACTH secretion). This article reviews data from human experiments which suggest that 11 beta-OHSD has tissue-specific actions which can increase or decrease sensitivity of both mineralocorticoid and glucocorticoid receptors to cortisol, and that assessment of cortisol sensitivity may prove equally important as assessment of cortisol secretion rates in hypertensive patients.
Steroids 1994 Feb
PMID:Organ-specific actions of 11 beta-hydroxysteroid dehydrogenase in humans: implications for the pathophysiology of hypertension. 819 53

Aldosterone production from 11-deoxycorticosterone was stimulated by hemin in primary cultures and homogenates of calf adrenal zona glomerulosa, in a time- and dose-dependent fashion. The ferrochelatase inhibitor 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) blocked the stimulation of aldosterone mediated by adrenocorticotropin (ACTH). Addition of hemin after treatment with DDC partially restored ACTH action. These results suggest that hemin may play a role in regulation of aldosterone production.
Steroids 1993 Aug
PMID:Stimulation of aldosterone production by hemin in calf adrenal glomerulosa cell cultures. 821 89

Stress induces an imbalance of neuroimmunomodulation, a phenomenon involving the immune, central nervous and endocrine systems. Receptors to substances involved in stress reactions and anxiety, like adrenaline, acetylcholine, histamine, endomorphines, ACTH and several neuropeptides, are present on lymphocytes and lymphocytes can secrete various hormones and neuropeptides. Peripheral and central, cortical and subcortical nervous structures influence immune response. Steroids play a dose dependent inhibitory role perhaps via GIF (Glucocorticoid Increasing Factor) and cytokines (IL 1). In rats, stress induces an increase of corticosterone levels and a lymphopenia depending on the presence of adrenals and pituitary, whereas functional responses to mitogens appear decreased in animals even after surgical removal of adrenals and/or pituitary. Immune response vary according to the degree of control over stressors, to the type of stressor and the animal species. Chronic or repeated stress tends to stimulate immune reaction, contrary to acute stress. In man grief reactions, terminal illness of a spouse, divorce, examinations, caregiving to Alzheimer patients have been used as models of stress, with immune consequences. Pathological anxiety has been less studied, with only few anomalies reported in DSM III-R panic disorder. The immune system participation in the adaptive response to stress is reviewed.
 ...
PMID:[Stress and panic. Immunologic aspects]. 828 94

In order to gain a better understanding of adrenal steroid production in guinea pigs, adrenocorticotropin (ACTH) was administered to castrated adult guinea pigs and a series of C-21 and C-19 steroid levels were determined in both adrenals and plasma over a 6-h period. After injection of ACTH, adrenal cortisol and corticosterone concentrations were stimulated by almost 40- and threefold, respectively, whereas the content of C-21 steroid precursors, namely pregnenolone, 17-hydroxypregnenolone, progesterone, and 17-hydroxyprogesterone, was stimulated by two- to 10-fold. Increases of C-19 steroid levels, namely dehydroepiandrosterone (DHEA), androstenedione (4-DIONE), testosterone, and 11 beta-hydroxyandrostenedione (11 beta-DIONE) ranging from 1.5 to eight times were also observed in the adrenals. In castrated guinea pigs, basal plasma DHEA, 4-DIONE, and testosterone levels were undetectable by radioimmunoassay, whereas 11 beta-DIONE concentrations were in a range similar to those in intact animals. In plasma, ACTH had a marked effect on corticosterone, cortisol, and 11 beta-DIONE. The present results indicate that although guinea pig adrenals synthesized several C-19 steroids, only 11 beta-DIONE was secreted by the adrenals into circulation even after administration of ACTH. The biological activity of this hydroxylated C-19 steroid was then assessed by using silastic implants in castrated guinea pigs, and it was shown that plasma 11 beta-DIONE concentrations increased by threefold and had no effect on prostate weight. Moreover, by using ZR-75-1 cells, a mammary cancer cell line extremely sensitive to androgens, we demonstrated that 11 beta-DIONE had an androgenic potency 35-fold less than that of dihydrotestosterone.
Steroids 1993 Jan
PMID:Effects of adrenocorticotropin on adrenal and plasma 11 beta-hydroxyandrostenedione in the guinea pig and determination of its relative androgen potency. 838 68

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.
Steroids 1995 Sep
PMID:Radioimmunoassay of three deoxycorticoids in human plasma following HPLC separation. 854 50

A method was developed for the estimation of levels of cortisol-21-sulfate (F KS), cortisone-21-sulfate (ES), and 20(alpha + beta)-reduced cortisol-21-sulfates in blood plasma. Levels of these conjugates were determined in peripheral vein plasma of 42 normal subjects, 21 men, and 21 women (age range 20-64 years) and in adrenal vein plasma of patients with various adrenocortical disorders, six patients with primary hyperaldosteronism, five patients with Cushing's syndrome, and in two obese patients, suspected to have Cushing's syndrome, but with inconclusive laboratory findings. Adrenal vein blood was obtained by percutaneous, trans-femoral adrenal vein catheterization. Levels of non-conjugated (free) cortisol were determined in all plasma samples along with those of the sulfated steroids. F kappa S was found in all plasma samples, both in men and women. The variation in F kappa S levels paralleled that in the free cortisol levels, thus the ratio of F kappa/F kappa S was the same in the blood samples drawn at 8 AM as in those drawn at 4 PM or 5 PM (ranges: 17.5-36.3 in men, 23.6-45.8 in women). The levels of F kappa S were relatively lower in women than in men (women 610-880 ng/100 mL at AM, 300-510 ng/100 mL at PM; men: 760-1,220 ng/100 mL at AM, 380-760 ng/100 mL at PM). Plasma levels of total sulfate-conjugated delta 4-3-keto-C-21 steroids (F kappa S + E kappa S + 20(alpha+beta)-dihydrocortisol-21-sulfates) were 30-40% higher than those of the levels of cortisol-21-sulfate alone (separated by thin-layer chromatography). In the adrenal vein plasma, levels of delta 4-3-keto-C-21-steroid-21-yl sulfates were 20 to 40 times higher than levels of these steroids in the peripheral blood. The bulk of the steroid sulfate measured in the adrenal vein plasma consisted of cortisol-21-sulfate. The ratio of F kappa/F kappa S in the adrenal vein plasma was markedly smaller than in the peripheral vein plasma; it was 6.9-12.3 in males and 4.9-6.7 in females, whereas in the peripheral vein of the same subjects it was 19.2-43.7 in males and 21.4-48.3 in females. Cortisol-21-sulfate isolated from adrenal vein plasma was identified by mass spectrometry. The data presented provide evidence for the secretion of this conjugate by the adrenal cortex. Its secretion appears to be markedly elevated in patients with Cushing's syndrome, both due to hyperplasia and due to adrenal adenoma, as compared with normal subjects and patients with primary aldosteronism, both males and females. However, the F kappa/F kappa S ratio was markedly lower in Cushing's patients due to adrenal adenoma than due to adrenal hyperplasia, this suggesting that ACTH is stimulating intra-adrenal hydrolysis of cortisol sulfate.
Steroids 1995 Dec
PMID:Corticosteroids in human blood: IX. Evidence for adrenal secretion of sulfate-conjugated cortisol, 11 beta,17 alpha-dihydroxy-4-pregnene-3,20-dione-21-yl-sulfate. 865 Jul 5

Using cultured bovine adrenal fasciculata cells (BAC), we investigated the effects of two hormones, corticotropin (ACTH) and angiotensin II (Ang-II) and two growth factors, insulin-like growth factors I (IGF-I) and transforming growth factor beta 1 (TGF beta 1), on the mRNA levels of nuclear proto-oncogenes of the Fos and Jun families and on the mRNA levels of genes expressed in BAC coding for ACTH and AT1 receptors, cytochrome P450scc and P450 17 alpha and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). ACTH and IGF-1 increased c-fos and jun-B mRNA levels early with later increases in the levels of mRNA for the ACTH receptor and the three steroidogenic enzymes, and enhanced steroidogenic responses to both ACTH and Ang-II. In contrast, Ang-II increased mRNA coding for the three proto-oncogenes (cfos, c-jun, and jun-B), decreased those for P450 17 alpha and 3 beta-HSD, and caused marked homologous and heterologous steroidogenic desensitization. TGF beta 1 increased only jun-B mRNA and markedly reduced BAC-differentiated functions and steroidogenic responsiveness to both ACTH and Ang-II. The long-term effects of ACTH on human adrenal fasciculata cells were comparable with those observed in BAC, whereas the long term effects of Ang-II and TGF beta 1 were different from those observed in BAC. Whether these species-specific differences are related to a different effect of these factors on proto-oncogene expression is not yet known.
Steroids 1996 Apr
PMID:Regulation of primary response and specific genes in adrenal cells by peptide hormones and growth factors. 873 96

Recent studies have demonstrated that the interconversion of active and inactive glucocorticoids plays a key role in determining the specificity of the mineralocorticoid receptor and controlling local tissue glucocorticoid receptor activation. Two distinct isoforms of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) have been identified. 11 beta-HSD1 is NADPH-dependent and at its major site of action (the liver) is a reductase, converting cortisone to cortisol (11-dehydrocorticosterone to corticosterone in the rat). 11 beta-HSD2 is NAD-dependent, is present in tissues such as the kidney and placenta, and converts cortisol to cortisone (corticosterone to 11-dehydrocorticosterone in the rat). Congenital or acquired deficiency of 11 beta-HSD2 produces the syndrome of apparent mineralocorticoid excess (SAME) in which cortisol gains access to the unprotected nonspecific mineralocorticoid receptor. The congenital deficiency is associated with mutations in the gene encoding the kidney isoform of 11 beta-HSD2; the acquired form results from inhibition of the enzyme by licorice, carbenoxolone, ACTH-dependent steroids in the ectopic ACTH syndrome, and possibly circulating inhibitors of the enzyme. This paper focuses on recent evidence, which suggest that low levels of placental 11 beta-HSD2 result in increased exposure of the fetus to maternal glucocorticoid and low birth weight. In animal studies using the rat we have shown that birth weight is correlated positively and placental weight negatively with the level of placental 11 beta-HSD. Thus animals with low birth weight and large placentae were those likely to be exposed to the highest level of maternal glucocorticoid. In man a similar relationship was found with birth weight being significantly correlated either with placental 11 beta-HSD activity or with the extent of cortisol inactivation by isolated perfused placental cotyledons. Administration of dexamethasone (which is poorly metabolized by placental 11 beta-HSD2) to pregnant rats resulted in decreased birth weight and the development of hypertension in the pups when adult. The same results were obtained when pregnant rats were given carbenoxolone, an inhibitor of placental 11 beta-HSD2. Low protein diet during pregnancy in the rat resulted in low birth weight of the pups, increased placental weight but decreased placental 11 beta-HSD activity, and adult hypertension. Thus increased glucocorticoid exposure of the fetus secondary to a failure of the normal inactivation of maternal glucocorticoid by the placental may be an important mechanism linking changes in the in utero environment and common adult diseases.
Steroids 1996 Apr
PMID:11 beta-Hydroxysteroid dehydrogenases: key enzymes in determining tissue-specific glucocorticoid effects. 873 12

The present study was undertaken to examine the mechanism whereby beta-lipotropin stimulates adrenal steroidogenesis. In guinea pig adrenal cells, beta-lipotropin (10(-8) M) increased basal steroid production 6-, 4-, and 5-fold for cortisol, androstenedione, and dehydroepiandrosterone (DHEA), respectively, whereas the corresponding responses to adrenocorticotropin (ACTH) (10(-9) M) were 12-, 8-, and 7-fold. The conversion of cholesterol to pregnenolone was studied in cells treated with trilostane, an inhibitor of 3 beta-hydroxysteroid delta 4-5 isomerase. beta-Lipotropin (10(-10) and 10(-8) M) and ACTH (10(-9) M) stimulated pregnenolone production in trilostane-treated cells. The production of cortisol and androgens from precursor steroids was also studied in cells treated with aminoglutethimide, an inhibitor of cholesterol side chain cleavage, after addition of exogenous pregnenolone, 17-hydroxypregnenolone, progesterone, or DHEA. Neither ACTH nor beta-lipotropin stimulated cortisol, androstenedione, or DHEA production in the presence of exogenous precursors in aminoglutethimide-treated cells. No inhibition of the beta-lipotropin- or ACTH-stimulated cortisol or androstenedione responses was demonstrated with the opioid receptor antagonist naloxone (10(-11) to 10(-5) M). The results suggest that beta-lipotropin stimulates steroidogenesis by acting on the conversion of cholesterol to pregnenolone and that its effects are not mediated via an opioid receptor but may be mediated via an ACTH receptor.
Steroids 1996 May
PMID:beta-Lipotropin-stimulated adrenal steroid production. 873 40


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