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PubMedDate not supplied

Effect of cold exposure on testicular delta 5-3 beta and 17 beta hydroxysteroid dehydrogenase activities and plasma levels of testosterone in toad (Bufo melanostictus) in breeding and hibernating season: duration-dependent response.

The purpose of this study was to show the effect of cold exposure on testicular activities in breeding and hibernating seasons in the toad. Adult male toads were placed in a cold chamber in both breeding and hibernating seasons for periods of 7, 14 and 21 days. At the time of sacrifice on the 15th and 22nd days, cold-exposed animals showed a decrease in testicular weight, testicular delta 5-3 beta and 17 beta-hydroxysteroid dehydrogenase activities and low levels of plasma testosterone both in breeding and hibernating seasons. There was no significant alteration in the above mentioned steroidogenic enzymes and plasma levels of testosterone after 7 days of cold exposure, both in breeding and hibernating seasons in respect to the control animals. The results of our present experiment suggest that environmental cold is an important modulator of breeding activities in the male toad. It also indicates that the breeding and hibernating cycle in the toad (seasonal breeders) may be asynchronous to each other.

17-Hydroxysteroid Dehydrogenases↗
PubMed1992

The heterogeneity of 11-beta-hydroxysteroid dehydrogenase activities in the rat hippocampus implies a complex regulation of steroid hormone action.

1. The rat hippocampus 11-beta-hydroxysteroid dehydrogenase (11-HSD) displays a different substrate specificity to that of other tissues. S1 nuclease analysis was used to determine whether the hippocampal messenger RNA is different from that found in other tissues. 2. S1 nuclease analysis using probes spanning the full length cDNA demonstrated that there were no differences in sequence between the hippocampal 11-HSD and the enzyme originally cloned from the liver. 3. These results suggest that there may be multiple 11-HSD isoforms in the hippocampus with different substrate specificities.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1993

11 beta-Hydroxysteroid dehydrogenase activity in mesenteric arteries of spontaneously hypertensive rats.

1. 11 beta-Hydroxysteroid dehydrogenase (11-HSD) activity in mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was determined and expressed as the percentage conversion of [3H]-corticosterone to [3H]-11-dehydrocorticosterone. 2. 11-HSD activity was significantly decreased in mesenteric arteries of both 4 and 9 week old SHR (8.4 +/- 0.8%, 5.0 +/- 1.5%, respectively) compared with WKY rats (12.4 +/- 0.6%, 15.8 +/- 0.7%, respectively; P < 0.05). 3. Total RNA from rat vascular smooth muscle cells (VSMC) and endothelial cells (EC) were prepared with selective precipitation in 3 mol/L LiCl/6 mol/L urea. The expression of 11-HSD mRNA was confirmed in the rat VSMC but its mRNA expression was not detected in EC, using northern blot analysis. 4. The results in this study indicate that 11-HSD in the vascular wall may play a role in the pathogenesis of hypertension in SHR.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Vascular localization of the 11 beta-hydroxysteroid dehydrogenase type II enzyme.

1. The enzyme 11 beta-hydroxysteroid dehydrogenase type II (11 beta HSD2) confers specificity on the non-specific mineralocorticoid receptor by converting cortisol to cortisone. 2. We have examined the localization of this enzyme in the human skin, myocardium and saphenous vein by immunohistochemical techniques. 3. High amounts of 11 beta HSD2 immunoreactivity were found in smooth muscle cells in the arterioles of the skin, heart and saphenous vein. Lower amounts of staining were also found in longitudinal and concentric smooth muscle cells lining the lumen of the saphenous vein.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1982

Subcellular distribution of 3 alpha-hydroxysteroid dehydrogenase and antiestrogen action on androgen-metabolizing enzymes in rat pituitary gland.

Gonadectomy of male rats led to a threefold increase of 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSDH) activity in pituitary homogenates that could be completely reversed by chronic administration of estradiol or 5 alpha-dihydrotestosterone (DHT). 3 alpha-HSDH was found to be distributed mainly between the 10,000 g and 100,000 g sediments from whole homogenates. The microsomal enzyme activity showed a substantial specificity for NADH whereas the cytosolic enzyme (100,000 g supernatant) demonstrated a slight preference for NADPH. The changes in Vmax found in homogenates following gonadectomy and gonadal steroid administration reflected changes in NADH-linked activity of the microsomal, but not the cytosolic enzyme. Estradiol-induced suppression of NADH-linked 3 alpha-HSDH activity in pituitary homogenates from gonadectomized rats of either sex was accompanied by a similar suppression of NADPH-linked 5 alpha-reductase activity and a marked decrease of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release. In the ovariectomized rat chronic administration of nonsteroidal antiestrogens had strong estrogenic effects on 3 alpha-HSDH activity and LH release, but not on 5 alpha-reductase activity and FSH release. In the gonadectomized male rat, which was much less sensitive to intrinsic estrogenicity of the antiestrogens tested, nafoxidine completely blocked estradiol-induced suppression of 5 alpha-reductase activity and FSH release and partially antagonized suppression of LH release. The trans-isomeric, substituted triphenylethylenes, tamoxifen, and enclomiphene, as well as nitromifene (mixture of trans and cis isomers) were able partially to counteract estradiol-induced suppression of 5 alpha-reductase, but not 3 alpha-HSDH activity. It is concluded that estradiol action on pituitary 5 alpha-reductase, but not 3 alpha-HSDH activity, involves an estrogen receptor mechanism.

3-Hydroxysteroid Dehydrogenases↗
PubMed1984

3 alpha-Hydroxysteroid oxidoreductase in rat brain.

We describe a simple procedure for the microassay of 3 alpha-hydroxysteroid oxidoreductase in homogenates of rat brain. This enzyme converts dihydrotestosterone to 3 alpha-androstandiol. We have mapped the distribution of the enzymatic activity in 14 regions of the rat brain. The highest activities were observed in homogenates of olfactory bulb (51/nmol/mg protein/h) and olfactory tubercle (29 nmol/mg protein/h). Substantially lower values were seen in the other brain regions, including thalamus, caudate nucleus, frontal cortex, hippocampus, hypothalamus, and preoptic area (6-20 nmol/mg protein/h).

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

A novel 11 beta-hydroxysteroid dehydrogenase inhibitor contained in saiboku-to, a herbal remedy for steroid-dependent bronchial asthma.

To identify the inhibitor of prednisolone metabolism contained in Saiboku-To, we conducted in-vitro experiments of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), using rat liver homogenate and cortisol as a typical substrate. We studied the effects of ten herbal constituents on 11 beta-HSD. Five herbal extracts showed inhibitory activity with Glycyrrhiza glabra > Perillae frutescens > Zizyphus vulgaris > Magnolia officinalis > Scutellaria baicalensis. This suggests that unknown 11 beta-HSD inhibitors are contained in four herbs other than G. glabra which contains a known inhibitor, glycyrrhizin (and glycyrrhetinic acid). Seven chemical constituents which have been identified as the major urinary products of Saiboku-To in healthy and asthmatic subjects were studied; magnolol derived from M. officinalis showed the most potent inhibition of the enzyme (IC50, 1.8 x 10(-4) M). Although this activity was less than that of glycyrrhizin, the inhibition mechanism (non-competitive) was different from a known competitive mechanism. These results suggest that magnolol might contribute to the inhibitory effects of Saiboku-To on prednisolone metabolism through inhibition of 11 beta-HSD.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Activation of 11 beta-hydroxysteroid dehydrogenase by dehydroepiandrosterone sulphate as an anti-hypertensive agent in spontaneously hypertensive rats.

The anti-hypertensive properties of dehydroepiandrosterone sulphate (DHEAS) have been investigated by studying its effects on blood pressure, on serum concentrations of corticosterone and dehydrocorticosterone, and on 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity in spontaneously hypertensive rats (SHR). SHR were given intraperitoneal injections of DHEAS (10 mg day-1 for 70 days) from six to 16 weeks of age. The blood pressure-time curve was significantly (P < 0.05) suppressed immediately after administration of DHEAS. There was no difference between the heart rates of control and DHEAS groups. Serum concentrations of corticosterone and dehydrocorticosterone in the DHEAS group were significantly (P < 0.05) lower than those of the control group. The dehydrocorticosterone/corticosterone concentration ratio was, however, significantly (P < 0.05) higher in the DHEAS group, suggesting that treatment with DHEAS enhanced the overall interconversion of corticosterone to dehydrocorticosterone. The activity of 11 beta-HSD in specific organs of the DHEAS group was affected, characteristic changes being increases in the kidney (14-58%), decreases in the liver (11-27%) and no change in the testis. Direct addition of DHEAS to 11 beta-HSD preparations from the kidneys of control SHR had the same effect as that observed in the in-vivo experiments. The fall in serum corticosterone in the DHEAS group is considered to be related, at least partly, to increased activity of kidney 11 beta-HSD. The inverse correlation of kidney 11 beta-HSD activity with serum corticosterone and blood pressure (-r = 0.628, P < 0.01, and -r = 0.478, P < 0.05, respectively) suggest that DHEAS delayed the development of hypertension in SHR by selective promotion of kidney 11 beta-HSD activity which in turn resulted in lower serum concentrations of corticosterone and its minimal aldosterone-like activity.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2003

Is 11beta-hydroxysteroid dehydrogenase type 1 a therapeutic target? Effects of carbenoxolone in lean and obese Zucker rats.

In liver and adipose tissue, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates glucocorticoids from inactive 11-keto metabolites. Pharmacological inhibition or transgenic disruption of 11beta-HSD1 attenuates glucocorticoid action and increases insulin sensitivity. Increased adipose 11beta-HSD1 may also contribute to the metabolic complications of obesity. Here, we examine the effects of inhibition of 11beta-HSDs with carbenoxolone in obese insulin-resistant Zucker rats, a strain in which tissue-specific dysregulation of 11beta-HSD1 (increased in adipose, decreased in liver) mirrors changes in human obesity. Six-week-old male rats were treated orally with carbenoxolone (50 mg/kg/day) or water (1 ml/kg/day) for 3 weeks. Carbenoxolone inhibited 11beta-HSD1 activity in liver (25 +/- 3 versus 52 +/- 2% conversion in lean; 18 +/- 3 versus 35 +/- 3% in obese; p < 0.01) but not in adipose tissue or skeletal muscle. Carbenoxolone had no effect on weight gain or food intake, did not affect plasma glucose during an oral glucose tolerance test, and increased the plasma insulin response to glucose. However, high-density lipoprotein cholesterol was increased by carbenoxolone in obese animals (1.52 +/- 0.24 versus 1.21 +/- 0.26 mM; p < 0.03). Carbenoxolone did not inhibit hepatic inactivation of glucocorticoid by 5beta-reductase and had no significant effect on plasma corticosterone levels. In conclusion, carbenoxolone provides a model for liver-specific inhibition of 11beta-HSD1, which results in improved lipid profile, in Zucker obese rats. Failure to inhibit 11beta-HSD1 in adipose tissue and/or skeletal muscle may explain the lack of effect on glucose tolerance and obesity. Inhibition of adipose 11beta-HSD1 is probably necessary to gain the maximum benefit of an 11beta-HSD1 inhibitor.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed1979

Bile salt 3 alpha- and 12 alpha-hydroxysteroid dehydrogenases from Eubacterium lentum and related organisms.

Thirty-two strains of Eubacterium lentum and phenotypically similar anaerobic gram-positive bacilli were screened for intracellular bile salt 3alpha- and 12alpha-hydroxysteroid dehydrogenase (HSDHase) activities. These organisms were categorized into four groups: (A) those containing 12alpha-HSDHase only (10 strains), (B) those containing 3alpha- and 12alpha-HSDHase (13 strains), (C) those containing 3alpha-HSDHase only (2 strains), and (D) those devoid of any measurable HSDHase activity (7 strains). Of the respective four groups, 9/10, 13/13, 0/2, and 0/7 were like the neotype strain of E. lentum (ATCC 25559) in that they produced H(2)S in a triple sugar iron agar butt, reduced nitrate to nitrite, and weakly decomposed hydrogen peroxide. The other strains were variable for nitrate reduction and activity on hydrogen peroxide, but all the organisms in the first three categories (with one exception) were H(2)S producers (triple sugar iron agar butt) and all (with one exception) were designated E. lentum, whereas the organisms of category B were non-H(2)S producers (triple sugar iron agar butt). Five of these seven were not stimulated by arginine and are designated "phenotypically similar organisms." Thin-layer chromatography of extracted spent bacterial medium of four representative strains from each group grown in the presence of cholate revealed the presence of (A) 12-oxo product, (B) 12-oxo and 3-oxo products, (C) 3-oxo product, and (D) the absence of any of these products. The 12alpha-HSDHase of category B organisms was unstable unless 10(-3) M dithioerythritol was added to the buffer. With the exception of 3 out of 32 strains, there was a positive correlation between the production of measurable amounts of 12alpha-HSDHase and H(2)S production. Growth curves and the effect of arginine on growth and the production of 3alpha- and 12alpha-HSDHase were examined in representative strains of categories A, B, and C. Both enzymes were shown to bind onto a nicotinamide adenine dinucleotide-Sepharose column and could be eluted by high-ionic-strength buffer, resulting in approximately 25-fold and 18-fold purification, respectively. Molecular weight estimations by Sephadex G-200 gave values of 205,000 and 125,000 for the 3alpha- and 12alpha-HSDHase, respectively. Purified 12alpha-HSDHase was investigated with respect to pH requirement, substrate specificity, and enzyme kinetics.

3-Hydroxysteroid Dehydrogenases↗
PubMed2006

Corticosterone impairs the mRNA expression and activity of 3beta- and 17beta-hydroxysteroid dehydrogenases in adult rat Leydig cells.

Clinical and experimental studies, including our own observations, have shown the adverse effects of excess glucocorticoids on testicular steroid hormone production. The present study was designed to gain insight into the molecular mechanisms by which excess corticosterone impairs Leydig cell steroidogenesis. To achieve this, adult rats were administered with corticosterone-21-acetate (2 mg/100 g body weight) twice daily for 15 days. After the treatment period, rats were killed by decapitation. The testes were removed, decapsulated aseptically and used for the isolation of Leydig cells. Purified Leydig cells were used for assessing the activity of 3beta- and 17beta-hydroxysteroid dehydrogenases (HSDs) and total RNA isolation. For in vitro studies, purified Leydig cells (7.5 x 10(6) cells) of control rats were plated in culture flasks and exposed to different concentrations (50, 100, 200, 400, and 800 nmol/L) of corticosterone for 24 h. At the end of incubation, total RNA was isolated from cultured Leydig cells, and the mRNA of 3beta- and 17beta-HSDs was quantified by RT-PCR. A significant reduction in the activities and levels of 3beta-HSD type-I and 17beta-HSD type-III mRNAs in Leydig cells were observed. In vitro studies demonstrated a dose-dependent significant impairment in both the activity and mRNA expression of these enzymes. These results suggest that corticosterone might have a direct effect on the transcription of the genes of 3beta- and 17beta-HSD. It is inferred from the present in vivo and in vitro studies that one of the molecular mechanisms by which excess corticosterone decreases the steroidogenic potency of Leydig cells is by suppressing the mRNA expression of 3beta-HSD type-I and 17beta-HSD type-III enzymes.

17-Hydroxysteroid Dehydrogenases↗
PubMed2006

Effect of stress on hepatic 11beta-hydroxysteroid dehydrogenase activity and its influence on carbohydrate metabolism.

Stress activates the synthesis and secretion of catecholamines and adrenal glucocorticoids, increasing their circulating levels. In vivo, hepatic 11beta-hydroxysteroid dehydrogenase 1 (HSD1) stimulates the shift of 11-dehydrocorticosterone to corticosterone, enhancing active glucocorticoids at tissue level. We studied the effect of 3 types of stress, 1 induced by bucogastric overload with 200 mmol/L HCl causing metabolic acidosis (HCl), the second induced by bucogastric overload with 0.45% NaCl (NaCl), and the third induced by simulated overload (cannula), on the kinetics of hepatic HSD1 of rats and their influence on the activity of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, glycemia, and glycogen deposition. Compared with unstressed controls, all types of stress significantly increased HSD1 activity (146% cannula, 130% NaCl, and 253% HCl), phosphoenolpyruvate carboxykinase activity (51% cannula, 48% NaCl, and 86% HCl), and glycemia (29% cannula, 30% NaCl, and 41% HCl), but decreased hepatic glycogen (68% cannula, 68% NaCl, and 78% HCl). Owing to these results, we suggest the following events occur when stress is induced: an increase in hepatic HSD1 activity, augmented active glucocorticoid levels, increased gluconeogenesis, and glycemia. Also involved are the multiple events indirectly related to glucocorticoids, which lead to the depletion of hepatic glycogen deposits, thereby contributing to increased glycemia. This new approach shows that stress increments the activity of hepatic HSD1 and suggests that this enzyme could be involved in the development of the Metabolic Syndrome.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed1995

NAD-dependent 11 beta-hydroxysteroid dehydrogenase in cultured human colonic epithelial cells.

The inactivation of physiological glucocorticoids by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) confers mineralocorticoid specificity to certain aldosterone target tissues. However, 11 beta-HSD activity in a human mineralocorticoid-responsive tissue has never been characterized. The present studies describe the features of 11 beta-HSD in the cultured human colonic epithelial cell line, T84. The 11 beta-HSD activity of T84 cells resided in the microsomal fraction and showed a marked preference for NAD rather than NADP as cofactor. NAD or NADP (200 microM) increased the conversion of corticosterone to 11-dehydrocorticosterone by 24.1 +/- 2.1 and 0.5 +/- 0.7 pmol.mg protein-1.20 min-1, respectively, indicating a > 40-fold preference for NAD vs. NADP. The Michaelis constant values for corticosterone and cortisol were 11.3 +/- 1.5 and 79.8 +/- 10 nM, respectively. The T84 11 beta-HSD was inhibited by 11-dehydrocorticosterone in a noncompetitive fashion [inhibition constant (Ki) = 180 +/- 9.6 nM] and by carbenoxolone in a competitive fashion (Ki = 17.4 +/- 1.3 nM). The expression of mineralocorticoid receptors in these cells was demonstrated by reverse transcriptase-polymerase chain reaction of mRNA isolated from T84 cells and by [3H]aldosterone binding studies. The coexpression of this NAD-dependent isoform of 11 beta-HSD and mineralocorticoid receptors is consistent with the view that the NAD-dependent isoform is responsible for the specificity of mineralocorticoid responses.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2005

11Beta-hydroxysteroid dehydrogenase type 2 and the regulation of surfactant protein A by dexamethasone metabolites.

Glucocorticoid (GC) metabolism by the 11beta-hydroxysteroid dehydrogenase (HSD) system is an important prereceptor regulator of GC action. The HSD enzymes catalyze the interconversion of the endogenous, biologically active GC cortisol and its inactive 11-dehydro metabolite cortisone. The role of the HSD enzymes in the metabolism of synthetic GCs, such as dexamethasone (Dex), is more complex. The human lung is a classic GC-sensitive organ; however, the roles of the HSD enzymes (HSD1 and HSD2) in the human lung are poorly understood. In the present study, we examined the expression of the HSD enzymes in human adult and fetal lung tissues and the human lung epithelial cell line NCI-H441. We observed that human adult and fetal lung tissues, as well as H441 cells, express HSD2 protein and that it is upregulated by Dex (10(-7) M). By contrast, HSD1 protein was undetectable. We also show that the Dex-mediated regulation of surfactant protein A is attenuated by inhibition of HSD2 activity. Furthermore, we demonstrate that unlike the inactive, 11-dehydro metabolite of cortisol (i.e., cortisone), the 11-dehydro metabolite of Dex, 11-dehydro-Dex, competes for binding to the GC receptor (GR) in human lung epithelial cells and retains GR agonist activity. Together, these data suggest that differences exist in the biological activities of the metabolites of cortisol and Dex.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed1993

11 beta-hydroxysteroid dehydrogenase and corticosteroid hormone receptors in the rat colon.

In the rat kidney 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) maintains normal in vivo specificity for mineralocorticoid receptor (MR) by converting the active steroid corticosterone to inactive 11-dehydrocorticosterone, leaving aldosterone to occupy the MR. Clinical observations support the hypothesis that 11 beta-HSD also protects the distal colonic MR from glucocorticoid excess. We have measured 11 beta-HSD mRNA and activity along the rat colon and have analyzed the distribution of 11 beta-HSD, MR, and glucocorticoid receptor (GR) mRNA within rat distal colon using in situ hybridization. Levels of 11 beta-HSD mRNA (1.7 and 3.4 kb) and activity were higher in distal vs. proximal colon, paralleling reported MR mRNA levels. Within the distal colon mucosa both 11 beta-HSD immunoreactivity and mRNA was observed in cells in the lamina propria but not in epithelial cells. MR mRNA was present in surface epithelial cells, but was also colocalized with the same 11 beta-HSD-expressing cells in the lamina propria. In contrast GR mRNA was more uniformly distributed. The localization of MR mRNA to nonepithelial cells in the lamina propria, possibly neuroendocrine cells, suggests that mineralocorticoid-regulated sodium transport across colonic epithelial cells may also involve a paracrine mechanism. As with the kidney, exposure of active mineralocorticoid to the MR in these cells in the lamina propria is dictated by 11 beta-HSD in an autocrine fashion.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

11 beta-Hydroxysteroid dehydrogenase in the rat inner ear.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) was demonstrated specifically in the spiral ligament of the cochlear membranous labyrinth by enzyme assay, Western blotting, and immunocytochemistry. Other cochlear regions and the vestibular membranous labyrinth were devoid of 11 beta-HSD. Spiral ligament 11 beta-HSD exerted predominantly an oxidative activity and was NADP specific, which is similar to 11 beta-HSD in most other tissues. 11 beta-HSD was colocalized with mineralocorticoid and glucocorticoid steroid receptors in the spiral ligament. 11 beta-HSD may control steroid binding to these inner ear steroid receptors and, in addition, may regulate steroid receptor binding in the adjacent stria vascularis in paracrine fashion.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Glycyrrhetinic acid-induced apoptosis in thymocytes: impact of 11beta-hydroxysteroid dehydrogenase inhibition.

It has been proposed that glycyrrhetinic acid (GA) enhances endogenous glucocorticoid (GC) action by suppressing the metabolism of the steroid. We show here that marked involution of the thymus occurred within 24 h of a single intraperitoneal administration of GA in mice. Thymocytes from mice treated with GA exhibited DNA cleavage and mitochondrial transmembrane potential disruption, as demonstrated with agarose gel electrophoresis and flow cytometric analysis. Immunocytochemical staining revealed that CD4(+)CD8(+) double positive cells markedly decreased after GA treatment. In contrast to GA in vivo, GA in vitro did not induce apoptosis of cultured thymocytes. These findings suggest that the apoptosis-inducing effect of GA on thymocytes is due to its indirect action. Because GA has been known to inhibit 11beta-hydroxysteroid dehydrogenase (11beta-HSD), we measured the enzyme activity in major organs and endogenous corticosterone concentration after GA treatment. The results showed a significant decrease of 11beta-HSD activity (P < 0.0001) and an increase in serum corticosterone concentration (P < 0.005). We concluded that the inhibition of hepatic 11beta-HSD activity by GA has a serious effect on GC metabolism, which results in a significant elevation of systemic GC levels. Apoptosis of thymocytes occurred as a consequence of the elevation in the level of endogenous corticosterone.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Corticosteroid receptors and 11beta-hydroxysteroid dehydrogenase isoforms in rat intestinal epithelia.

To evaluate the potential roles that both receptors and enzymes play in corticosteroid regulation of intestinal function, we have determined glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) expression in intestinal epithelial cells. GR and MR mRNA and receptor binding were ubiquitously expressed in epithelial cells, with receptor levels higher in ileum and colon than jejunum and duodenum. RNase protection analysis showed that 11beta-HSD1 was not expressed in intestinal epithelial cells, and enzyme activity studies detected no 11-reductase activity. 11beta-HSD2 mRNA and protein were demonstrated in ileal and colonic epithelia; both MR and GR binding increased when enzyme activity was inhibited with carbenoxolone. Duodenal and jejunal epithelial cells showed very little 11beta-HSD2 mRNA and undetectable 11beta-HSD2 protein; despite minor (<7%) dehydrogenase activity in these cells, enzyme activity did not alter binding of corticosterone to either MR or GR. These findings demonstrate the ubiquitous but differential expression of MR and GR in intestinal epithelia and that 11beta-HSD2 modulates corticosteroid binding to both MR and GR in ileum and proximal and distal colon but not in duodenum or jejunum.

11-beta-Hydroxysteroid Dehydrogenases↗