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Query: UMLS:C0338671 (Steroids)
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The urinary excretion of 3beta,16beta-dihydroxy-5-androsten-17-one (16beta-OH-DHEA) is increased in patients with low renin essential hypertension. This steroid and its isomer 3beta,17beta-dihydroxy-5-androsten-16-one (16-oxo-A) have also been reported to have mineralocorticoid activity in adrenalectomized rats. These findings have led to the postulate that excessive secretion of 16beta-OH-DHEA may be responsible for the production of low renin essential hypertension. In this study unilaterally nephrectomized salt loaded rats injected once a week with 30 mg of 11-desoxycorticosterone acetate per/kg of body weight for 2 month periods developed hypertension. Rats given similar amounts of 16beta-OH-DHEA or 16-oxo-A and rats given no steroids did not develop hypertension. We conclude that it is unlikely that 16beta-OH-DHEA and 16-oxo-A are direct causative factors in the production of low renin essential hypertension.
Steroids 1977 Jan
PMID:Blood pressure changes following chronic administration to rats of 3beta,16beta-dihydroxy-5-androsten-17-one, 3beta,17beta-dihydroxy-5-androsten-16-one and 21-hydroxy-4-pregnene-3,20-dione-21-acetate. 13 80

18,19-Dihydroxycorticosterone (18,19(OH)2-B) and 18-hydroxy-19-norcorticosterone (18-OH-19-nor-B) measurements were carried out on the urine of patients with primary aldosteronism (PA), essential hypertension (EHT), and liver cirrhosis with (LC, SA (+)) and without (LC, SA (-)) aldosteronism. The separation of these steroids was performed by extraction and high-performance liquid chromatography followed by radioimmunoassay (RIA) with specific antibodies prepared in our laboratory. 18,19(OH)2-B excretion was elevated in patients with PA (24 +/- 5.9 [+/- SE] micrograms/24 hr; n = 15) and LC, SA (+) (83 +/- 9.4 micrograms/24 hr; n = 8). Values in LC, SA (-) (3.1 +/- 1.2 micrograms/24 hr; n = 8) and in EHT (3.7 +/- 0.4 micrograms/24 hr; n = 42) were found to be similar to those in normal subjects (5.5 +/- 0.9 micrograms/24 hr; n = 30). The values of urinary 18-OH-19-nor-B in PA and LC, SA (+) were higher than in LC, SA (-) EHT and normal subjects (P less than 0.05). Values in the latter three groups, as compared with each other, did not show significant alterations. Nothing is known about the biologic relevance of 18,19(OH)2-B and very little about that of 18-OH-19-nor-B, but the latter steroid seems to potentiate experimental renal hypertension. One can speculate about possible roles of both steroids as precursors of other steroids, e.g., the biologically potent mineralocorticoid 19-noraldosterone. The data obtained suggest that it is not relevant to measure the urinary levels of either steroid in these clinical syndromes.
Steroids 1991 Nov
PMID:Urinary 18,19-dihydroxycorticosterone and 18-hydroxy-19-norcorticosterone excretion in patients with primary and secondary aldosteronism. 181 24

The activities of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) and 5 beta-reductase were analyzed in 39 normotensive controls and 128 patients with essential hypertension. The activity of 11 beta-HSD was obtained by dividing the 24-hour urinary tetrahydrocortisone by the sum of tetrahydrocortisol (THF) and allotetrahydrocortisol (aTHF), whereas the activity of 5 beta-reductase was obtained by dividing the 24-hour urinary THF by aTHF. The activity of 5 beta-reductase was significantly lower in essential hypertensives compared with normotensive controls (P < 0.05). However, the activity of 11 beta-HSD did not differ between normotensive controls and essential hypertensives. A positive correlation between the activities of 11 beta-HSD and 5 beta-reductase was observed in essential hypertensives (r = 0.60, P < 0.01). Neither 11 beta-HSD nor 5 beta-reductase activity correlated with indices of renal mineralocorticoid receptor activation, which were assessed by determination of plasma potassium and urinary excretion of sodium as well as potassium. Taken together, these results suggest that disturbances of one of the inactivation pathways of cortisol may contribute to the pathogenesis of hypertension.
Steroids 1994 Nov
PMID:The activities of 5 beta-reductase and 11 beta-hydroxysteroid dehydrogenase in essential hypertension. 770 42

There is emerging evidence that cortisol plays a significantly greater role in human hypertension than previously thought. Apart from the well recognized role of cortisol in the hypertension of Cushing's syndrome, local cortisol excess has been recognized as responsible for rare forms of hypertension such as apparent mineralocorticoid excess and licorice abuse and more recently implicated in the hypertension of chronic renal failure, hypertension related to low birth weight and essential hypertension. Although cortisol-induced hypertension is characterized by sodium retention and volume expansion, studies with synthetic glucocorticoids or sodium restriction suggest that the hypertension is, to a substantial degree, independent of sodium and volume. Increase in cardiac output is not essential for cortisol-induced blood pressure rise but the precise role of increases in total or regional peripheral resistance as a primary mechanism has nto been determined. Increased pressor responsiveness, particularly to catechols, is a prominent feature but whether these changes are sufficient to account for the hypertension remains unclear. There is no evidence for increased sympathetic nervous activity as judged by measurements of plasma catcholamines, neuropeptide-Y, or resting noradrenaline spillover rate. Responses to mental stress or maximal hand-grip are unchanged and baroreflex sensitivity is increased. Octreotide profoundly reduced the elevated plasma insulin concentrations seen with cortisol administration but had no effect on the rise in blood pressure.
Steroids 1995 Jan
PMID:Mechanisms of cortisol-induced hypertension in humans. 779 21

Investigators in hypertension have extensively evaluated the mechanisms of hypertension as first described by Goldblatt in his classic clipped kidney models. Although renovascular hypertension appears to affect only 2-4% of the population referred for diagnostic studies of hypertension, our understanding of renovascular hypertension has broadened from the interaction of the renin-angiotensin system to the inclusion of the activation of the sympathetic nervous system and locally mediated prostaglandins. This increased understanding of renal mediated abnormalities has also led to the implication that abnormalities in renal function may be the main abnormality in primary hypertension. It has been demonstrated that early, mildly hypertensive patients may have an increase in total body volume. This elevated volume may lead to autoregulation which persistently elevates vascular resistance. The renal abnormality leading to an abnormal pressure-volume relationship may be related to a decrease in renal plasma flow mediated by an increase in arteriolar resistance. This increase in vascular tone has been ascribed to an increase in sympathetic nerve activity, an increase in renin and/or an increase in catechols and angiotensin II. It has also been suggested that ischemic nephrons in a microvascular model akin to the classic Goldblatt two kidney-one clip model may be the pathologic abnormality underlying primary hypertension. These concepts of renovascular hypertension and primary renal dysfunction are reviewed in this conference.
Steroids 1993 Dec
PMID:Mechanisms of renal hypertension and renal contribution to primary hypertension. 811 14

Mean mineralocorticoid receptor number in mononuclear leukocytes of patients with increased plasma aldosterone (Conn's syndrome, nephrovascular hypertension, preeclampsia) is lower than in controls and this reduction could be the consequence of a down-regulation of the receptor. A similar pattern is evident also in situations of excess of other mineralocorticoids (Cushing's syndrome, chronic licorice ingestion). In essential hypertension 20% of cases have reduced number of mineralocorticoid receptors in mononuclear leukocytes without increase of aldosterone and normal serum potassium. We postulate that in some cases with essential hypertension the reduction of mineralocorticoid receptors is an index of mineralocorticoid excess due to mineralocorticoids other than aldosterone.
Steroids 1993 Dec
PMID:Regulation of aldosterone receptors in hypertension. 811 17

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

We have previously reported that 5 alpha and 5 beta pathways of steroid metabolism are controlled in vivo by dietary Na+ and glycyrrhetinic acid, see Gorsline et al. 1988; Latif et al. 1990. The present investigations provide evidence supporting the suggestion that endogenous substances may regulate the glucocorticoid inactivating isoenzymes, 11 beta-HSD (hydroxysteroid dehydrogenase) 1 (liver) and 11 beta-HSD2 (kidney). The activity of 11 beta-HSD is impaired in essential hypertension, following licorice ingestion, and in patients with apparent mineralocorticoid excess where 11 beta-HSD2 is particularly affected. In all three conditions, excretion of the less common 5 alpha metabolites is elevated in urine. We now report on the differential abilities of a series of Ring A reduced (5 alpha and 5 beta) adrenocorticosteroid and progesterone metabolites to inhibit these isoenzymes. Using liver microsomes with NADP+ as co-factor (11 beta-HSD1), and sheep kidney microsomes with NAD+ as co-factor (11 beta-HSD2), we have systematically investigated the abilities of a number of adrenocorticosteroids and their derivatives to inhibit the individual isoforms of 11 beta-HSD. A striking feature is the differential sensitivity of the two isoenzymes to inhibition by 5 alpha and 5 beta derivatives. 11 beta-HSD1 is inhibited by both 5 alpha and certain 5 beta derivatives. 11 beta-HSD-2 was selectively inhibited only by 5 alpha derivatives: 5 beta derivatives were without inhibitory activity toward this isoform of 11 beta-HSD. These results indicate the importance of the structural conformation of the A and B Rings in conferring specific inhibitory properties on these compounds. In addition, we discuss the effects of additions or substitutions of other functional groups on the inhibitory potency of these steroid molecules against 11 beta-HSD1 and 11 beta-HSD2.
Steroids 1997 Feb
PMID:Selective inhibition of sheep kidney 11 beta-hydroxysteroid dehydrogenase isoform 2 activity by 5 alpha-reduced (but not 5 beta) derivatives of adrenocorticosteroids. 905 82

The infusion of 40 mEq potassium (aspartate) in 250 ml isotonic 1-fructose at a rate of 20 mEq/h into 5 patients (34-56 years old) with aldosteronoma and 2 patients with bilateral primary aldosteronism consistently raised their mean arterial pressure by 15-20 mmHg. Their pressure values returned to the baseline levels 4-5 h after the infusion. In contrast, in controls (10 patients with idiopathic arterial hypertension, matched for age, sex, and magnitude of the untreated hypertension, and 7 patients with inactive adrenal nodules as incidental findings on upper abdomen ultrasound or computerized tomography) the same procedure caused negligible arterial pressure changes. The cause of the rise in blood pressure observed uniquely in patients with primary aldosteronism after infusion of potassium (aspartate) cannot be accounted for by an increase in plasma aldosterone, blood volume, or plasma angiotensin II. The cause of this response thus remains obscure; nonetheless, this simple procedure may prove useful in differentiating primary aldosteronism from idiopathic hypertension, in excluding the adrenal disorder, and in revealing even its mildest forms.
Steroids 1999 Apr
PMID:An easy diagnostic approach to primary aldosteronism. 1039 87

The aims of this study were to search for the role of cholic acid in the regulation blood pressure of humans and rats and to investigate the effects of cholic acid on the production of vascular aldosterone and corticosterone in rats. Levels of serum total bile acids were measured by an enzymic spectrophotometeric method in normal controls, patients with essential hypertension, and in Wistar and spontaneously hypertensive rats. Levels in essential hypertension (7.3+/-3.4 micromol/l, n = 88) were higher than those of normal subjects (4.9+/-3.3 micromol/l, n = 86), and levels in SHR (13.9+/-3.8 micromol/l, n = 11) were slightly increased, but not significantly different from Wistar rats (10.4+/-5.1 micromol/l, n = 12). Male Wistar rats received cholic acid 80 mg/kg/day, orally, for 30 days, and blood pressure was monitored by a pressure transducer. Systolic blood pressure increased in Wistar rats treated with cholic acid compared to control rats. Mesenteric artery perfusion ex vivo was performed, and pressor responses to norepinephrine were determined in Wistar rats. The pressor responses to norepinephrine in mesenteric arteries treated with cholic acid were significantly increased. The perfusate from the mesenteric arteries was collected and applied to a Sep-Pak C 18 cartridge column for reverse phase high performance liquid chromatography, and levels of both aldosterone and corticosterone were determined by radioimmunoassay. Levels of aldosterone were decreased but those of corticosterone increased in the perfusate from arteries treated with cholic acid. Reverse transcriptase polymerase chain reaction showed that cholic acid inhibited the expression of 11beta-HSD2 and CYP11B2 mRNA in mesenteric arteries. These results reveal that cholic acid is able to induce hypertension and provide evidence that cholic acid inhibits the transcription of both 11beta-HSD2 and CYP11B2 in vasculature, leading to lower aldosterone and higher corticosterone production in vessels and increased vasoconstrictor responses to norepinephrine.
Steroids 1999 Apr
PMID:Effects of cholic acid on blood pressure and production of vascular aldosterone and corticosterone. 1039 86


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