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At least 721 records · Page 40Linked to original sources
PubMed1994

Decreased activity of 11 beta-hydroxysteroid dehydrogenase in mesenteric arteries of Dahl salt-sensitive rats.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) activity in mesenteric arteries of 4-week- and 8-week-old Dahl rats was determined to evaluate the relationship between glucocorticoids and norepinephrine in hypertension, 11 beta-HSD activity (expressed as the percentage conversion of 3H-corticosterone (B) to 3H-11-dehydrocorticosterone (A)) significantly decreased in 8-week-old Dahl salt-sensitive (DS) rats (11.4 +/- 1.4%) compared with Dahl salt-resistant (DR) rats (15.3 +/- 0.3%) (p < 0.05) when each group was fed a high-sodium chow (7%) for 4 weeks. There were no significant differences in 11 beta-HSD activity in the 4-week-old DS and DR rats. The enhanced response of mesenteric arteries to norepinephrine was observed only in 8-week-old DS rats. Our results suggest that a decreased 11 beta-HSD activity in the vascular walls contributes to the increased response of norepinephrine by local increment of glucocorticoids in DS hypertensive rats.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Expression of 11 beta-hydroxysteroid dehydrogenase mRNA in rat vascular smooth muscle cells.

The enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD) converts corticosterone to the inactive 11-dehydrocorticosterone in the rat. The bioactivity of 11-HSD, expressed as the percentage conversion of 3H-corticosterone to 3H-11-dehydrocorticosterone, was 13.7 +/- 0.4% in rat vascular smooth muscle cells (rVSMC). Cells treated with 100 nM dexamethasone (Dex) showed a 1.4-fold (p < 0.05) increase in 11-HSD activity. Insulin (100 microM) decreased 11-HSD activity by 0.8-fold (p < 0.05). Expression of 11-HSD mRNA was also confirmed in rVSMC by Northern blot analysis. Dexamethasone increased and insulin decreased the levels of 11-HSD mRNA in parallel with the increase in bioactivity. Vascular smooth muscle cells express 11-HSD activity; the access of corticosterone to vascular smooth muscle receptors may be modulated by the enzyme.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Distribution of 11 beta-hydroxysteroid dehydrogenase along the rat intestine.

Aldosterone selectivity of mineralocorticoid target tissues has been suggested to be due to the inactivation of glucocorticoids in the target tissue by 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD). The distribution of 11 beta-OHSD was studied in the intestine which is composed of aldosterone-sensitive and insensitive segments. The activity of the enzyme was high in distal colon and medium in ileum, cecum, and proximal colon. Zero activity was found in duodenum and jejunum. Carbenoxolone completely blocked the enzyme. Low-salt diet increased the activity in proximal colon and decreased in ileum. Adrenalectomy decreased the activity in ileum and proximal colon. The existence of segmental differences in the distribution of 11 beta-OHSD and the hormonal effect on the activity of the enzyme suggest a physiological role of 11 beta-OHSD in the intestine.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Effect of growth hormone, insulin and dexamethasone on 11 beta-hydroxysteroid dehydrogenase activity on a primary culture of rat hepatocytes.

11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) is a microsomal enzyme present in the peripheral tissues of the rat, including the liver, and is mediated by a number of factors in animal in vivo studies. However, the effect of peptide hormones and glucocorticoids on the activity of 11 beta-HSD in isolated rat hepatocytes is not clear. To investigate these effects, we determined 11 beta-HSD activity in a primary culture of rat hepatocytes by adding various concentrations of growth hormone, insulin and dexamethasone (Dex). 11 beta-HSD activity increased significantly after treatment with Dex (10(-9)M-10(-6)M) for 48h. Dex (100nM) treated hepatocytes, incubated for 12h to 48h, resulted in a significant two-to four-fold rise in 11 beta-HSD activity compared to control (p < 0.01), which was in contrast to GH (10(-9)M-10(-6)M) and insulin (10(-8)M-10(-5)M), which inhibited 11 beta-HSD activity (p < 0.05). These results suggest that the 11 beta-HSD of rat hepatocytes is under multifactorial regulation; Dex stimulates and GH and insulin inhibit 11 beta-HSD activity in primary cultures of rat hepatocytes.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Intra-adrenal 11 beta-hydroxysteroid dehydrogenase plays a role in the regulation of corticosteroid secretion: an in vitro study in the rat.

The expression of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) has been demonstrated in the adrenal glands, but until now little attention has been paid on its possible physiologic action. In-situ perfused rat adrenals released under basal conditions, in addition to mineralo- and glucocorticoids, notable amounts of 11-dehydrocorticosterone (DH-B), the inactive form to which corticosterone (the main glucocorticoid in rodents) is converted by 11 beta-HSD. The addition to the perfusion medium of glycyrrhetinic acid, a specific inhibitor of 11 beta-HSD, strongly reduced DH-B release and simultaneously evoked a moderate rise in both mineralo- and glucocorticoid output. The bolus administration of ACTH strikingly enhanced mineralo- and glucocorticoid secretion, but it significantly depressed DH-B release Rat adrenal microsome preparations possessed 11 beta-HSD activity, that was inhibited by glycyrrhetinic acid. Conversely, ACTH was without any apparent effect, a finding indicating that the in vivo observed ACTH-induced inhibition of adrenal 11 beta-HSD activity is mediated by an indirect mechanism whose elucidation requires further investigation. In conclusion, our present findings suggest that adrenal 11 beta-HSD plays a role in the regulation of steroid secretion in rats under both basal and stimulated conditions.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1993

Acute reduction of renal 11 beta-hydroxysteroid dehydrogenase activity by several antinatriuretic stimuli.

The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity of the kidney prevents access of cortisol or corticosterone to the renal mineralocorticoid receptor. Reduction of 11 beta-HSD activity by nutritional, hormonal, or pharmacologic factors might enhance the mineralocorticoid effect of these corticosteroids, thus causing sodium retention. To test this concept, we studied the effect on 11 beta-HSD activity of several antinatriuretic factors given orally to rats or exposed in vitro to rat renal tissue. Renal 11 beta-HSD activity was higher in fasted than fed rats (P < .05). Glucose, ethanol, and Toradol (Syntex Laboratories, Palo Alto, CA) given orally to fasted rats all reduced renal 11 beta-HSD activity by 20% to 40% (P < .05-.005) to levels similar to those observed in fed animals. Incubation of renal tissue from fasted rats with physiologic concentrations of insulin, ethanol, and Toradol also reduced 11 beta-HSD activity by 20% to 40% (P < .05-.01). These findings are consistent with the hypothesis that the antinatriuretic actions of these stimuli are due in part to alteration of renal 11 beta-HSD leading to greater mineralocorticoid effects in kidney.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1980

Estradiol 17 beta-dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase from human placental cytosol: one enzyme with two activities?

The soluble enzyme estradiol 17 beta-dehydrogenase (17 beta-ED) from human term placental cytosol is reported to be a stereospecific oxidoreductase for estrogen substrates. A published purification scheme (heat treatment and affinity chromatography) yielded a homogeneous protein which had the reported characteristics of pure 17 beta-ED and also had 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activity. Spectrophotometric assay when the buffer contained albumin, 8 mg/ml, masked the 20 alpha-HSD activity observed in albumin-free conditions and may explain why this bifunctional activity has gone unrecognized. In human placenta, one enzyme may catalyze stereospecific oxidation/reduction of both estrogen and progesterone.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Corticosteroid 11 beta-hydroxysteroid dehydrogenase activities in vertebrate liver.

In this paper, we examine corticosteroid 11 beta-oxidation and 11-reduction as properties of the microsomal 11 beta-hydroxysteroid dehydrogenase complex in vertebrate livers. No hepatic activity in the oxidative direction (11 beta -dehydrogenase) was found in the frog, toad, mud puppy, shark, and bird livers. In contrast, all mammalian livers had active oxidizing enzymes. Latency, defined as microsome-linked activity released by the detergent Triton DF-18, was a property of 11 beta-dehydrogenase in all mammalian livers. Mammal, bird, and dogfish livers reduced 11-dehydrocorticosteroids (11-reductase), while amphibians and bony fish did not. With the exception of rat liver, latency was a property of all the mammalian liver 11-reductases examined.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1992

Effects of carbenoxolone administered acutely to adrenalectomized rats (in vivo) on renal and hepatic handling of corticosterone by 11 beta-hydroxysteroid dehydrogenase.

The in vivo effect(s) of carbenoxolone (CS) on renal 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD), hepatic 11 beta-OHSD, and 5 beta-reductase enzymatic activity was investigated, under conditions previously shown to confer mineralocorticoid (MC)-like activity on the glucocorticoids cortisol and corticosterone; it has been suggested that this Na+ retention is linked to inhibition of renal 11 beta-OHSD. The results show that acute administration of CS [2.5 mg/rat for 0.5 or 2 hours; and 10 or 25 mg/rat for 2 hours subcutaneously (sc)] to rats caused no inhibition of 11 beta-OHSD activity in kidney homogenates, minces, and microsomes when compared with controls. However, addition of 50 nM CS to the incubation medium completely inhibited the 11 beta-OHSD activity in kidney homogenates and microsomes (from controls or CS-injected rats). In contrast, hepatic microsomal 11 beta-OHSD was significantly inhibited after in vivo treatment with CS (P < 0.05) using 2 microM and 50 microM corticosterone, as was 5 beta-reductase (P < 0.05) using 4 microM corticosterone as substrate. However, chronic glycyrrhizin administration (15 mg/rat/day sc for 14 days) significantly inhibited renal 11 beta-OHSD activity when assayed in minces or homogenates. Thus, it appears that when CS is administered acutely, its effects are primarily on hepatic 11 beta-OHSD and 5 beta-reductase with no inhibition of renal 11 beta-OHSD.(ABSTRACT TRUNCATED AT 250 WORDS)

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1993

Inhibition by glycyrrhetinic acid of rat tissue 11 beta-hydroxysteroid dehydrogenase in vivo.

Inhibition of 11 beta-hydroxysteroid dehydrogenase (11-HSD) in the major organs of the rat by the inhibitor glycyrrhetinic acid (a component of licorice) was investigated. The inhibitor decreased 11-HSD levels in most organs after intraperitoneal injection. The effect was dose dependent, was maximally effective 3 hours after administration, and was completely reversed at 24 hours. The magnitude and patterns of effectiveness differed between tissues. It was concluded that the inhibition of 11-HSD by glycyrrhetinic acid is not restricted to one or a few organs, but is broadly based.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Functional studies of 11 beta-hydroxysteroid dehydrogenase.

11 beta-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the interconversion of cortisol and cortisone. This activity is postulated to protect the type I (mineralocorticoid) receptor from excessive concentrations of cortisol, allowing aldosterone to function as a mineralocorticoid. An enzyme with 11-HSD activity was isolated from rat liver and the corresponding rat and human cDNA and genomic clones isolated. This enzyme is a member of the "short chain dehydrogenase" family. Using site-directed mutagenesis, it was demonstrated that two highly conserved residues, Tyr-179 and Lys-183, are required for enzymatic function. Elimination of the amino terminus or the two glycosylation sites also destroys enzymatic activity. This may be due to actual disruption of enzymatic function or to effects on intracellular localization or stability of the enzyme. Examination of patients with apparent mineralocorticoid excess, a syndrome of juvenile hypertension thought to represent 11-HSD deficiency, did not reveal any mutations in the gene for this enzyme. There is substantial evidence for a second 11-HSD isozyme with distinct kinetic properties that is expressed in the renal distal tubule and possibly other sites of mineralocorticoid action. Apparent mineralocorticoid excess may involve this enzyme.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Bidirectional activity of 11 beta-hydroxysteroid dehydrogenase in vascular smooth muscle cells.

Endogenous glucocorticoids (GC) can be metabolized through the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD); in the rat, corticosterone (B) is converted to its inactive metabolite 11-dehydrocorticosterone (A). Since increased tissue concentrations of GCs may affect blood pressure by potentiating the vasoactive effects of alpha-adrenergic agonists and possibly other pressors, we studied the metabolism of corticosterone in freshly dissected aortae and cultured vascular smooth muscle cells (VSMC). Incubations were generally conducted for 60 min with 10(-8) M steroid; steroids were isolated and identified by HPLC. In aortic minces stripped of endothelium, the oxo-reductase reaction of A back to B was nearly 4 times greater than the dehydrogenase reaction of B to A (2.8 +/- 0.5 x 10(-11) versus 7.3 +/- 1.0 x 10(-12) mol/mg protein). This pattern was also seen in cultured VSMC during growth and quiescent states (growth A to B 3.2 +/- 0.4 x 10(-12) versus B to A 9.7 +/- 0.9 x 10(-13) mol/mg protein; quiescent A to B 8.8 +/- 0.1 x 10(-12) versus B to A 1.2 +/- 0.2 x 10(-12) mol/mg protein). Enzyme activity in either direction was less during growth, correlating with a decrease in mRNA for 11 beta-OHSD. In cell homogenates containing 200 microM NADP(H), the enzyme functioned equally in either direction at pH 7.4 with an apparent Km for corticosterone of approximately 2 x 10(-7) M. Carbenoxolone, an inhibitor of 11 beta-OHSD, suppressed the dehydrogenase reaction to a greater degree than the reverse oxo-reductase reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

The activities of 5 beta-reductase and 11 beta-hydroxysteroid dehydrogenase in essential hypertension.

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.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Organ-specific actions of 11 beta-hydroxysteroid dehydrogenase in humans: implications for the pathophysiology of hypertension.

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.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

11 beta-Hydroxysteroid dehydrogenase activity and corticosteroid hormone action.

In normal physiology 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) protects the mineralocorticoid receptor (MR) from glucocorticoid excess. In the rat, however, 11 beta-OHSD mRNA and activity is widespread, suggesting that it may also play a role in regulating ligand access to the glucocorticoid receptor (GR). We have studied the role of the 11 beta-OHSD in modulating corticosteroid hormone action in rat pituitary GH3 cells (glucocorticoids inhibit prolactin gene transcription) and renal epithelial NRK-52E cells (mineralocorticoids increase Na-K ATPase subunit gene expression) in culture. Both cell lines express high levels of 11 beta-OHSD activity, and Northern/Western blot analyses using a rat cDNA probe and antisera raised against rat liver 11 beta-OHSD reveal a single 1.4 Kb mRNA encoding an enzyme of molecular size 34 kDa. In GH3 cells, prolactin gene transcription was unaffected by corticosterone (B) in doses of 10(-8) to 10(-6) M. When 11 beta-OHSD activity was inhibited with the licorice derivative, glycyrrhetinic acid (GE); however, 10(-6) M B inhibited prolactin (PRL) mRNA levels to the same degree as an equimolar concentration of the GR agonist RU 28362. This effect was blocked by co-incubation with the GR antagonist RU 38486. In NRK-52E cells, co-incubation with B and GE resulted in a marked increase in alpha 1/beta 1 Na-K ATPase subunit mRNA levels when compared with GE and/or B alone and this effect could be blocked by administration of the MR antagonist RU 26752.(ABSTRACT TRUNCATED AT 250 WORDS)

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

11 beta-Hydroxysteroid dehydrogenase in renal collecting duct cells.

The purpose of this paper it to briefly review recent work from our laboratory dealing with the form of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) present in renal aldosterone target cells. It is well established that aldosterone is the physiological mineralocorticoid hormone. The observation that mineralocorticoid receptors have equal affinity for aldosterone and endogenous glucocorticoids, coupled with the fact that circulating levels of glucocorticoids are much higher than those of aldosterone, raises the question of how aldosterone can fulfill its function. To explain this paradox, it was hypothesized that in mineralocorticoid target tissues 11 beta-OHSD rapidly inactivates glucocorticoids (but not aldosterone), thereby decreasing intracellular glucocorticoid levels, so that aldosterone can exert specific regulation via the mineralocorticoid receptor. However, the only form of this enzyme which has been cloned thus far might not be the enzyme which is able to confer aldosterone selectivity on the mineralocorticoid receptor. On the other hand, a new form of 11 beta-OHSD (11 beta-OHSD/CD) that we have discovered in renal collecting duct cells possesses all the properties necessary for protecting the mineralocorticoid receptor: very high affinity for endogenous glucocorticoids, high abundance in target cells, and irreversible dehydrogenase activity. Our hypothesis is that 11 beta-OHSD/CD is the enzyme that ensures aldosterone selectivity in mineralocorticoid target cells, and that is the product of a gene different from the one previously cloned.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Genetic analysis of 11 beta-hydroxysteroid dehydrogenase.

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) catalyzes the interconversion of cortisol and cortisone. This activity is postulated to protect the Type I (mineralocorticoid) receptor from excessive concentrations of cortisol, allowing aldosterone to function as a mineralocorticoid. An enzyme with 11 beta-OHSD activity was isolated from rat liver and the corresponding rat and human cDNA and genomic clones isolated. This enzyme is a member of the short-chain dehydrogenase family. Using site-directed mutagenesis, it was demonstrated that the amino terminus and two highly conserved residues, Tyr-179 and Lys-183, are required for enzymatic function. Examination of patients with apparent mineralocorticoid excess, a syndrome of juvenile hypertension thought to represent 11 beta-OHSD deficiency, did not reveal any mutations in the HSD11 gene. This disorder may involve an additional enzyme with 11 beta-OHSD activity or possibly another cortisol metabolizing enzyme.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

3 Alpha-hydroxysteroid dehydrogenase activity in rat liver and skin.

3 alpha-Hydroxysteroid dehydrogenase (3 alpha HSD) is one of the main enzymes involved in the metabolism of the active androgen, dihydrotestosterone (DHT). 3 alpha HSD catalyzes the reversible reduction of DHT to 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha DIOL). The equilibrium of 3 alpha HSD reductive and oxidative activity is an important factor in the regulation of intracellular levels of DHT. In this study, we determined the kinetic characteristics of 3 alpha HSD in the subcellular fractions of female rat liver and abdominal skin. The enzyme expressed its activity in the cytosol and microsomal fractions of both of these tissues. It showed higher activity with the phosphorylated cofactors, NADPH and NADP, and was inhibited by indomethacin. The Vmax values of 3 alpha HSD in the cytosol were 10-fold higher than the Vmax values in the microsomes in both the liver and skin. In both tissues, the Km values with DHT as the substrate (reductive) were lower than the Km with 3 alpha DIOL as the substrate (oxidative). Although the Vmax values of the oxidative reaction were higher than the Vmax values of the reductive reaction in both liver and skin, the low Km values and the higher Vmax/Km ratio for DHT indicated that the reduction of DHT to 3 alpha DIOL was the favored reaction. The enzyme kinetics of 3 alpha HSD suggest that neither tissue accumulates DHT, but promptly converts it to 3 alpha DIOL.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗