DIFFERENCES IN SUBSTRATE AND INHIBITOR KINETICS OF HUMAN TYPE 1 AND TYPE 2 3β-HYDROXYSTEROID DEHYDROGENASE ARE EXPLAINED BY THE TYPE 1 MUTANT, H156Y

2002 ◽  
Vol 28 (4) ◽  
pp. 471-475 ◽  
Author(s):  
James L. Thomas ◽  
J. Ian Mason ◽  
Stacey Brandt ◽  
Wendy Norris
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Human Type ◽  
Kinetics Of ◽  
Inhibitor Kinetics

scholarly journals Expression of 11beta-hydroxysteroid dehydrogenase (11betaHSD) proteins in luteinizing human granulosa-lutein cells

2003 ◽  
Vol 178 (1) ◽  
pp. 127-135 ◽  
Author(s):  
LM Thurston ◽  
E Chin ◽  
KC Jonas ◽  
IJ Bujalska ◽  
PM Stewart ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Enzyme Activities ◽  
Hydroxysteroid Dehydrogenase ◽  
Steroid Synthesis ◽  
Western Blots ◽  
Human Type ◽  
Hek Cells

In a range of tIssues, cortisol is inter-converted with cortisone by 11beta-hydroxysteroid dehydrogenase (11betaHSD). To date, two isoforms of 11betaHSD have been cloned. Previous studies have shown that human granulosa cells express type 2 11betaHSD mRNA during the follicular phase of the ovarian cycle, switching to type 1 11betaHSD mRNA expression as luteinization occurs. However, it is not known whether protein expression, and 11betaHSD enzyme activities reflect this reported pattern of mRNA expression. Hence, the aims of the current study were to investigate the expression and activities of 11betaHSD proteins in luteinizing human granulosa-lutein (hGL) cells. Luteinizing hGL cells were cultured for up to 3 days with enzyme activities (11beta-dehydrogenase (11betaDH) and 11-ketosteroid reductase (11 KSR)) and protein expression (type 1 and type 2 11betaHSD) assessed on each day of culture. In Western blots, an immunopurified type 1 11betaHSD antibody recognized a band of 38 kDa in hGL cells and in human embryonic kidney (HEK) cells stably transfected with human type 1 11betaHSD. The type 2 11betaHSD antibody recognized a band of 48 kDa in HEK cells transfected with human type 2 11betaHSD cDNA but the type 2 protein was not expressed in hGL cells throughout the 3 days of culture. While the expression of type 1 11betaHSD protein increased progressively by 2.7-fold over 3 days as hGL cells luteinized, both 11betaDH and reductase activities declined (by 52.9% and 34.2%; P<0.05) over this same period. Changes in enzyme expression and activity were unaffected by the suppression of ovarian steroid synthesis.

Epigenetic regulation of established human type 1 versus type 2 cytokine responses

2008 ◽  
Vol 121 (1) ◽  
pp. 57-63.e3 ◽  
Author(s):  
Ruey-Chyi Su ◽  
Allan B. Becker ◽  
Anita L. Kozyrskyj ◽  
Kent T. HayGlass
Keyword(s):  
Epigenetic Regulation ◽  
Human Type ◽  
Cytokine Responses

scholarly journals 11?-Hydroxysteroid dehydrogenase Type 1 in obesity and Type 2 diabetes

Diabetologia ◽  
2004 ◽  
Vol 47 (1) ◽  
pp. 1-11 ◽  
Author(s):  
T. M. Stulnig ◽  
W. Waldh�usl
Keyword(s):  
Type 2 Diabetes ◽  
Hydroxysteroid Dehydrogenase

scholarly journals Human immunodeficiency virus types 1 and 2 have different replication kinetics in human primary macrophage culture

2006 ◽  
Vol 87 (2) ◽  
pp. 411-418 ◽  
Author(s):  
David Marchant ◽  
Stuart J. D. Neil ◽  
Áine McKnight
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Steady Rate ◽  
Immunodeficiency Virus ◽  
Load Characteristics ◽  
Kinetics Of ◽  
Hiv 1

This study compares the replication of primary isolates of human immunodeficiency virus type 2 (HIV-2) and type 1 (HIV-1) in monocyte-derived macrophages (MDMs). Eleven HIV-2 and five HIV-1 primary isolates that use CCR5, CXCR4 or both coreceptors to enter cells were included. Regardless of coreceptor preference, 10 of 11 HIV-2 viruses could enter, reverse transcribe and produce fully infectious virus in MDMs with efficiency equal to that in peripheral blood mononuclear cells. However, the kinetics of replication of HIV-2 compared with HIV-1 over time were distinct. HIV-2 had a burst of virus replication 2 days after infection that resolved into an apparent ‘latent state’ at day 3. HIV-1, however, continued to produce infectious virions at a lower, but steady, rate throughout the course of infection. These results may have implications for the lower pathogenesis and viral-load characteristics of HIV-2 infection.

scholarly journals Expression of Key Androgen-Activating Enzymes in Ovarian Steroid Cell Tumor, Not Otherwise Specified

2020 ◽  
Vol 8 ◽  
pp. 232470962093341
Author(s):  
Evana Valenzuela Scheker ◽  
Amita Kathuria ◽  
Ashwini Esnakula ◽  
Hironobu Sasano ◽  
Yuto Yamazaki ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Steroidogenic Enzymes ◽  
Androgen Excess ◽  
Ovarian Steroid ◽  
Variable Expression ◽  
Not Otherwise Specified ◽  
Chain Cleavage ◽  
Cleavage Enzyme

To characterize the expression of steroidogenic enzymes implicated in the development of ovarian steroid cell tumors, not otherwise specified (SCT-NOS). We present 4 ovarian SCT-NOS evaluated by immunohistochemical staining of steroidogenic enzymes as an approach to define this entity pathologically. All 4 ovarian SCT-NOS showed increased expression for cholesterol side-chain cleavage enzyme (CYP11A1), 17α-hydroxylase (CYP17A1), 17β-hydroxysteroid dehydrogenase 1 (HSD17B1), aldo-ketoreductase type 1 C3 (AKR1C3), 3β-hydroxysteroid dehydrogenase 2 (HSD3B2), 5α-reductase type 2 (SRD5A2), steroid sulfatase (SULT2A1), estrogen sulfotransferase (EST), and aromatase (CYP19A1). Expression was negative for 21-hydroxylase (CYP21A2) and 17β-hydroxysteroid dehydrogenase 2 (HSD17B2). 17β-hydroxysteroid dehydrogenase 3 (HSD17B3) and 5α-reductase type 1 (SRD5A1) showed variable expression. Our analysis reveals a novel finding of increased expression of AKR1C3, HSD17B1, SRD5A2, SULT2A1, and EST in ovarian SCT-NOS, which is clinically associated with androgen excess and virilization. Further studies are needed to validate these enzymes as new markers in the evaluation of hyperandrogenic ovarian conditions.

scholarly journals Characterization of cDNAs encoding isoforms of hamster 3 beta-hydroxysteroid dehydrogenase/delta 5-->4 isomerase

1998 ◽  
Vol 20 (1) ◽  
pp. 99-110 ◽  
Author(s):  
FM Rogerson ◽  
J Courtemanche ◽  
A Fleury ◽  
JG LeHoux ◽  
JI Mason ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Cdna Libraries ◽  
Sexually Dimorphic ◽  
High Affinity ◽  
Liver And Kidney ◽  
Low Levels ◽  
Type 3

Western blot analyses of various hamster tissues reveal high levels of expression of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in adrenal and liver, and moderate levels of expression in kidney. The expression in liver is sexually dimorphic; very high levels of protein are observed in adult male liver but very low levels are seen in the female liver. Three distinct cDNAs encoding isoforms of 3 beta-HSD were isolated from hamster cDNA libraries. The type 1 isoform is a high-affinity dehydrogenase/isomerase expressed in adrenal and male kidney. The type 2 isoform is also a high-affinity dehydrogenase/isomerase expressed in kidney and male liver. The type 3 enzyme is a 3-ketosteroid reductase expressed predominantly in kidney. Sequencing of the clones showed that all three are structurally very similar, although types 1 and 2 share the greatest degree of similarity. Immunohistochemical staining for 3 beta-HSD in the adrenal was found throughout the adrenal cortex. In the kidney staining was confined to tubules, and in the liver, heavy staining was found in hepatocytes. The cloning of cDNAs for 3 beta-HSD from the liver and kidney should help in elucidating the function of this enzyme in these tissues.

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.

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