scholarly journals N-glycosylation is not essential for enzyme activity of 11β-hydroxysteroid dehydrogenase type 2

1997 ◽  
Vol 52 (3) ◽  
pp. 682-686 ◽  
Author(s):  
Zhetcho N. Kyossev ◽  
W. Brian Reeves
Keyword(s):  
Enzyme Activity ◽  
Hydroxysteroid Dehydrogenase

scholarly journals Importance of the 11β-hydroxysteroid dehydrogenase enzyme in clinical disorders

2013 ◽  
Vol 154 (8) ◽  
pp. 283-293 ◽  
Author(s):  
Karolina Feldman ◽  
István Likó ◽  
Zsolt Nagy ◽  
Ágnes Szappanos ◽  
Vince Kornél Grolmusz ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Hydroxysteroid Dehydrogenase ◽  
Chromosome 1 ◽  
Gene Encoding ◽  
Local Synthesis ◽  
Dehydrogenase Enzyme ◽  
Clinical Disorders ◽  
Polymorphic Variants

Glucocorticoids play an important role in the regulation of carbohydrate and amino acid metabolism, they modulate the function of the immune system, and contribute to stress response. Increased and decreased production of glucocorticoids causes specific diseases. In addition to systemic hypo- or hypercortisolism, alteration of local synthesis and metabolism of cortisol may result in tissue-specific hypo- or hypercortisolism. One of the key enzymes participating in the local synthesis and metabolism of cortisol is the 11β-hydroxysteroid dehydrogenase enzyme. Two isoforms, type 1 and type 2 enzymes are located in the endoplasmic reticulum and catalyze the interconversion of hormonally active cortisol and inactive cortisone. The type 1 enzyme mainly works as an activator, and it is responsible for the generation of cortisol from cortisone in liver, adipose tissue, brain and bone. The gene encoding this enzyme is located on chromosome 1. The authors review the physiological and pathophysiological processes related to the function of the type 1 11β-hydroxysteroid dehydrogenase enzyme. They summarize the potential significance of polymorphic variants of the enzyme in clinical diseases as well as knowledge related to inhibitors of enzyme activity. Although further studies are still needed, inhibition of the enzyme activity may prove to be an effective tool for the treatment of several diseases such as obesity, osteoporosis and type 2 diabetes. Orv. Hetil., 2013, 154, 283–293.

17β-Hydroxysteroid dehydrogenase type 2 expression and enzyme activity in the human gastrointestinal tract

2001 ◽  
Vol 101 (5) ◽  
pp. 485 ◽  
Author(s):  
Toshikazu SANO ◽  
Gen HIRASAWA ◽  
Junji TAKEYAMA ◽  
Andrew D. DARNEL ◽  
Takashi SUZUKI ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Gastrointestinal Tract ◽  
Hydroxysteroid Dehydrogenase ◽  
Human Gastrointestinal Tract

scholarly journals Expression and Regulation of 11-β Hydroxysteroid Dehydrogenase Type 2 Enzyme Activity in the Glucocorticoid-Sensitive CEM-C7 Human Leukemic Cell Line

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-5
Author(s):  
Mark R. Garbrecht ◽  
Thomas J. Schmidt
Keyword(s):  
Enzyme Activity ◽  
Cell Line ◽  
Lymphoblastic Leukemia ◽  
Human Lymphocytes ◽  
Leukemic Cell ◽  
Hydroxysteroid Dehydrogenase ◽  
Leukemic Cell Line ◽  
Human Leukemic Cell ◽  
Human Leukemic Cell Line

Glucocorticoids are commonly used in the first-line treatment of hematological malignancies, such as acute lymphoblastic leukemia, due to the ability of these steroids to activate pro-apoptotic pathways in human lymphocytes. The goal of the current study was to examine the gene expression and enzyme activity of the microsomal enzyme, 11-β hydroxysteroid dehydrogenase type 2 (HSD11B2, HSD2), which is responsible for the oxidation of bioactive glucocorticoids to their inert metabolites. Using the glucocorticoid-sensitive human leukemic cell line, CEM-C7, we were able to detect the expression of HSD2 at the level of mRNA (via RT-PCR), protein (via immunohistochemistry and immunoblotting), and enzyme activity (via conversion of tritiated cortisol to cortisone). Furthermore, we observed that HSD2 enzyme activity is down regulated in CEM-C7 cells that were pretreated with the synthetic glucocorticoid, dexamethasone (100 nM, <15 hours), and that this down regulation of enzyme activity is blocked by the administration of the glucocorticoid receptor antagonist, RU-486. Taken collectively, these data raise the possibility that the effectiveness of glucocorticoids in the treatment of human leukemias may be influenced by: (1) the ability of these neoplastic cells to metabolize glucocorticoids via HSD2 and (2) the ability of these steroids to regulate the expression of this key enzyme.

scholarly journals Altered Activity of 11β-Hydroxysteroid Dehydrogenase Types 1 and 2 in Skeletal Muscle Confers Metabolic Protection in Subjects with Type 2 Diabetes

2007 ◽  
Vol 92 (8) ◽  
pp. 3314-3320 ◽  
Author(s):  
Christina Jang ◽  
Varuni R. Obeyesekere ◽  
Rodney J. Dilley ◽  
Zygmunt Krozowski ◽  
Warrick J. Inder ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Enzyme Activity ◽  
Vastus Lateralis ◽  
Hydroxysteroid Dehydrogenase ◽  
Significant Negative Correlation ◽  
University Teaching ◽  
Mrna Levels ◽  
Percent Conversion

Abstract Context: There is little information regarding the regulation of 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes in skeletal muscle in the setting of type 2 diabetes. Objective: Our objective was to investigate whether there is differential mRNA expression and enzyme activity of 11β-HSD1 and 11β-HSD2 in the skeletal muscle of diabetic subjects compared with controls at baseline and in response to dexamethasone. Design: Participants underwent muscle biopsy of vastus lateralis at baseline and after dexamethasone. Setting: The study took place at a university teaching hospital. Participants: Twelve subjects with type 2 diabetes and 12 age- and sex-matched controls participated. Intervention: Subjects were given oral dexamethasone, 4 mg/d for 4 d. Main Outcome Measures: We assessed 11β-HSD1, 11β-HSD2, and H6PDH mRNA levels by quantitative RT-PCR and enzyme activity by percent conversion of [3H]cortisone and [3H]cortisol, respectively. Results: At baseline, mRNA levels were similar in diabetic and control subjects for 11β-HSD1, 11β-HSD2, and H6PDH. 11β-HSD1 activity was reduced in diabetic subjects (percent conversion of [3H]cortisone to [3H]cortisol was 11.4 ± 2.5% vs. 18.5 ± 2.2%; P = 0.041), and 11β-HSD2 enzyme activity was higher in diabetic subjects (percent conversion of [3H]cortisone to [3H]cortisol was 17.2 ± 2.6% vs. 9.2 ± 1.3%; P = 0.012). After dexamethasone, 11β-HSD1 mRNA increased in both groups (P &lt; 0.001), whereas 11β-HSD2 mRNA decreased (P = 0.002). 11β-HSD1 activity increased in diabetic subjects (P = 0.021) but not in controls, whereas 11β-HSD2 activity did not change in either group. At baseline, there was a significant negative correlation between 11β-HSD1 and 11β-HSD2 enzyme activity (r = −0.463; P = 0.026). Conclusions: The activities of skeletal muscle 11β-HSD1 and 11β-HSD2 are altered in diabetes, which together may reduce intracellular cortisol generation, potentially conferring metabolic protection.

scholarly journals Characterization of 11beta-hydroxysteroid dehydrogenase activity and corticosteroid receptor expression in human osteosarcoma cell lines

1999 ◽  
Vol 161 (3) ◽  
pp. 455-464 ◽  
Author(s):  
R Bland ◽  
CA Worker ◽  
BS Noble ◽  
LJ Eyre ◽  
IJ Bujalska ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Cell Lines ◽  
Primary Cultures ◽  
Hydroxysteroid Dehydrogenase ◽  
Receptor Expression ◽  
Osteosarcoma Cell ◽  
Bone Homeostasis ◽  
Rt Pcr

Studies in vitro and in vivo have shown that corticosteroids play an important role in bone physiology and pathophysiology. It is now established that corticosteroid hormone action is regulated, in part, at the pre-receptor level through the expression of isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), which are responsible for the interconversion of hormonally active cortisol to cortisone. In this report we demonstrate 11beta-HSD activity in human osteoblast (OB) cells. Osteosarcoma-derived OB cell lines TE-85, MG-63 and SaOS-2 and fibrosarcoma Hs913T cells express the type 2 isoform of 11beta-HSD, as determined by reverse transcription polymerase chain reaction (RT-PCR) and specific enzyme assays. Enzyme activity was shown to be strictly NAD dependent with a Km of approximately 71 nM; 11beta-HSD type 1 mRNA expression and enzyme activity were not detected. All four cell lines expressed mRNA for the glucocorticoid receptor (GR) and mineralocorticoid receptor, but specific binding was only detectable with radiolabelled dexamethasone (Kd=10 nM) and not aldosterone. MG-63 cells had two to three times more GR than the other OB cells, which correlated with the higher levels of 11beta-HSD 2 activity in these cells. In contrast to the osteosarcoma cell studies, RT-PCR analysis of primary cultures of human OB cells revealed the presence of mRNA for 11beta-HSD 1 as well as 11beta-HSD 2. However, enzyme activity in these cells remained predominantly oxidative, i.e. inactivation of cortisol to cortisone (147 pmol/h per mg protein at 500 nM cortisol) was greater than cortisone to cortisol (10.3 pmol/h per mg protein at 250 nM cortisone). Data from normal human OB and osteosarcoma cells demonstrate the presence of an endogenous mechanism for inactivation of glucocorticoids in OB cells. We postulate that expression of the type 1 and type 2 isoforms of 11beta-HSD in human bone plays an important role in normal bone homeostasis, and may be implicated in the pathogenesis of steroid-induced osteoporosis.

THE INFLUENCE OF HAEMOGLOBIN-S AND G6PD DEFICIENCY ON THE ACTIVITY OF THE 17β-HYDROXYSTEROID DEHYDROGENASE OF INTACT HUMAN ERYTHROCYTES

1974 ◽  
Vol 75 (4) ◽  
pp. 793-800
Author(s):  
A. O. Sogbesan ◽  
O. A. Dada ◽  
B. Kwaku Adadevoh
Keyword(s):  
Enzyme Activity ◽  
Dehydrogenase Activity ◽  
Sex Steroids ◽  
G6pd Deficiency ◽  
Incubation Medium ◽  
Hydroxysteroid Dehydrogenase ◽  
G6pd Activity ◽  
Reverse Transformation ◽  
Oxidative Transformation ◽  
Haemoglobin S

ABSTRACT The 17β-hydroxysteroid dehydrogenase activity in intact erythrocytes of Nigerian patients, in particular with regard to haemoglobin genotypes and G6PD* activity was studied. The G6PD activity of the erythrocyte did not affect the oxidative transformation of testosterone to androstenedione and of oestradiol to oestrone. The reduction (reverse transformation) was inhibited in G6PD-deficient erythrocytes but this inhibition was offset by the addition of 0.025 m glucose to the incubation medium. The per cent oxidation transformation of testosterone was higher in Hb-AA than in Hb-SS erythrocytes. It is suggested that the differences may be a result of either lower enzyme activity in the Hb-SS erythrocytes or of differences in the uptake and possibly binding of sex steroids by intact Hb-SS and Hb-AA erythrocytes.

scholarly journals Synthesis, purification and crystallographic studies of the C-terminal sterol carrier protein type 2 (SCP-2) domain of human hydroxysteroid dehydrogenase-like protein 2

2015 ◽  
Vol 71 (7) ◽  
pp. 901-905 ◽  
Author(s):  
Zhong Cheng ◽  
Yao Li ◽  
Chun Sui ◽  
Xiaobo Sun ◽  
Yong Xie
Keyword(s):  
Catalytic Domain ◽  
Hydroxysteroid Dehydrogenase ◽  
Carrier Protein ◽  
Sterol Carrier Protein ◽  
X Ray Diffraction ◽  
Unit Cell Parameters ◽  
X Ray ◽  
Cell Parameters ◽  
Protein Molecules

Human hydroxysteroid dehydrogenase-like protein 2 (HSDL2) is a member of the short-chain dehydrogenase/reductase (SDR) subfamily of oxidoreductases and contains an N-terminal catalytic domain and a C-termianl sterol carrier protein type 2 (SCP-2) domain. In this study, the C-terminal SCP-2 domain of human HSDL2, including residues Lys318–Arg416, was produced inEscherichia coli, purified and crystallized. X-ray diffraction data were collected to 2.10 Å resolution. The crystal belonged to the trigonal space groupP3121 (orP3221), with unit-cell parametersa=b= 70.4,c= 60.6 Å, α = β = 90, γ = 120°. Two protein molecules are present in the asymmetric unit, resulting in a Matthews coefficient of 2.16 Å3 Da−1and an approximate solvent content of 43%.

11β Hydroxysteroid Dehydrogenase Type 2 in the Adrenal Gland by Testosterone Withdrawal of Adult Rats

Folia Medica ◽  
2010 ◽  
Vol 52 (2) ◽  
Author(s):  
Yvetta Koeva ◽  
Mariana Bakalska ◽  
Elisaveta Petrova ◽  
Nina Atanassova
Keyword(s):  
Adrenal Gland ◽  
Hydroxysteroid Dehydrogenase ◽  
Adult Rats
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