11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics* ; Humans ; Mineralocorticoid Excess Syndrome, Apparent/genetics* ; Pedigree

OBJECTIVE: To investigate the effects of calcium-sensitive receptors (CaSR) on the expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) and cortisol concentration in a neonatal mouse model of persistent pulmonary hypertension (PPH). METHODS: Fifty-six newborn C57BL/6 mice were randomly divided into a control group (n=14), a PPH group (n=14), an agonist group (n=14), and an inhibitor group (n=14). The mice in the PPH, agonist, and inhibitor groups were exposed to a 12% oxygen concentration, and the agonist group and inhibitor group were given CaSR agonist (GdCl3, 16 mg/kg) and CaSR antagonist (NPS2390, 1 mg/kg) intraperitoneally once a day, respectively. The mice in control group were exposed to air, and then injected with an equal volume of normal saline as those in the PPH group every day. All mice were treated for 14 days. Morphological examination of heart and lung tissues was performed using hematoxylin-eosin staining. The expression levels of 11β-HSD2 mRNA and 11β-HSD2 protein in lung tissues were measured by qRT-PCR and Western blot respectively. Brain natriuretic peptide (BNP) and cortisol levels in lung tissues were determined using ELISA. RESULTS: Compared with the control group, the PPH group had significantly increased pulmonary artery wall thickness (WT%), ratio of right to left ventricular thickness (RV/LV), alveolar mean linear intercept, and BNP concentration and a significantly reduced radial alveolar count (P<0.05); compared with the PPH group, the agonist group showed significant increases in WT% and BNP concentration, while the inhibitor group showed significant reductions in the two indicators (P<0.05). Compared with the control group, the PPH group showed significant reductions in the expression levels of 11β-HSD2 mRNA and 11β-HSD2 protein, but a significant increase in cortisol concentration (P<0.05); compared with the PPH group, the agonist group had significantly lower expression levels of 11β-HSD2 mRNA and 11β-HSD2 protein, but a significant higher cortisol concentration, while the inhibitor group showed opposite changes in these indicators (P<0.05). CONCLUSIONS CaSR may control the development and progression of PPH in newborn mice by regulating the expression of 11β-HSD2 and cortisol concentration.
11-beta-Hydroxysteroid Dehydrogenase Type 2 ; Animals ; Animals, Newborn ; Calcium ; Hydrocortisone ; Hypertension, Pulmonary ; Mice ; Mice, Inbred C57BL ; Receptors, Calcium-Sensing

OBJECTIVETo study the roles of type II 11&beta;-hydroxysteroid dehydrogenase (11&beta;-HSD2) and it's signaling factors in the lung tissue in pathogenesis of persistent pulmonary hypertension (PPH) in neonatal rats.

METHODSSix Sprague-Dawley rats on the 19th day of pregnancy were randomly divided into PPH and control groups (n=3 each). The PPH group was intraperitoneally injected with indomethacin (0.5 mg/kg) twice daily and exposed in 12% oxygen for three days, in order to prepare a fetal rat model of PPH. The control group was intraperitoneally injected with an equal volume of normal saline and exposed to air. Neonatal rats were born by caesarean section from both groups on the 22nd day of pregnancy. In each group, 15 neonatal rats were randomly selected and sacrificed. 11&beta;-HSD2 expression in the lung tissue of neonatal rats were observed by Confocal laser technology, and serum cortisol levels and prostacyclin, renin, angiotensin and aldosterone in the lung tissue of both groups were measured using ELISA.

RESULTS11&beta;-HSD2 protein was widely expressed in the lung tissue of the control and PPH groups. The levels of 11&beta;-HSD2 and prostacyclin in the lung tissue were lower in the PPH group than in the control group, while serum cortisol levels and renin, angiotensin and aldosterone in the lung tissue were higher in the PPH group than in the control group (P<0.05).

CONCLUSIONS11&beta;-HSD2 and it's signaling factors play roles in pathogenesis of PPH in neonatal rats.

11-beta-Hydroxysteroid Dehydrogenase Type 2 ; analysis ; physiology ; Animals ; Animals, Newborn ; Female ; Hypertension, Pulmonary ; enzymology ; etiology ; Male ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

This study was aimed to explore the expression of 11&beta;-hydroxysteroid dehydrogenase type 2 (11&beta;-HSD2) in 3 different lymphoblastic cell lines with relation to their glucocorticoid (GC) sensitivity. The 11&beta;-HSD2 expressions in acute lymphoblastic leukemia Jurkat cells, lymphoma Daudi and Raji cells, and peripheral blood T cells of a healthy volunteer were analyzed by real time PCR and Western blot. Glucocorticoid (GC)-induced apoptosis in 3 different cell lines was detected by flow cytometry. Cell growth in Jurkat cells treated with cortisol was analyzed by trypan blue dye exclusion. Flow cytometry was performed to observe GC-induced apoptosis in Jurkat cells treated by combination of GC with 11&beta;-HSD2 inhibition 18&beta;-glycyrrhetinic acid (18&beta;-GA). The results demonstrated that 11&beta;-HSD2 highly expressed in Jurkat cells, but not in Daudi, Raji cells and normal blood T cells. Compared to Daudi and Raji cells, Jurkat cells were more resistant to GC-induced apoptosis. Furthermore, the inhibition of 11&beta;-HSD2 by 18&beta;-GA resulted in increased cellular sensitivity to GC as shown by elevated induction of apoptosis. it is concluded that 11&beta;-HSD2 is at least partly responsible for GC resistance in Jurkat cells. 11&beta;-HSD2 may be a potential target for reduction of GC-resistance in therapeutic applications.
11-beta-Hydroxysteroid Dehydrogenase Type 2 ; metabolism ; Cell Line, Tumor ; Glucocorticoids ; pharmacology ; Glycyrrhetinic Acid ; analogs & derivatives ; pharmacology ; Humans ; Jurkat Cells ; Lymphocytes ; drug effects ; metabolism

OBJECTIVETo explore the relationship between HSD11B2 polymorphisms and fetal growth during normal pregnancy.

METHODSThe HSD11B2 promoter/G-209A, G-194C, G-151A and G-126A genotypes were examined in 33 samples from Chinese Han subjects by gene sequencing. HSD11B2 (CA)n microsatellite polymorphism in the first intron was detected in blood samples from 187 maternal and newborn pairs by PCR-capillary electrophoresis.

RESULTSAll the HSD11B2 promoter/G-209A, G-194C, G-151A and G-126A genotypes were wild-type GG. The offspring birth weight and any ultrasound parameters describing late gestational fetal body shape were not significantly different between maternal or fetal SS, SL and LL groups or combined SS+SL and LL groups. When considering the relevant confounding factors (gestational age at delivery, newborn's gender, maternal body mass index before pregnancy, maternal weight at delivery and maternal age), the offspring birth weight and late pregnancy ultrasound parameters were still not associated with the maternal or fetal HSD11B2 (CA) n microsatellite polymorphisms.

CONCLUSIONSFetal and maternal HSD11B2 polymorphism is not related to fetal growth during normal pregnancy.

11-beta-Hydroxysteroid Dehydrogenase Type 2 ; genetics ; Birth Weight ; Body Mass Index ; Female ; Fetal Development ; genetics ; Genotype ; Gestational Age ; Humans ; Infant, Newborn ; Polymorphism, Genetic ; Pregnancy ; Promoter Regions, Genetic

OBJECTIVETo study the association between phthalate esters (PAEs) metabolites in maternal urine and 11beta-hydroxysteroid dehydrogenase type 2 (11&beta;-HSD2 ) enzyme activity, explore the possible mechanism of PAEs effect on fetal development.

METHODSAll of 33 cases of intrauterine growth retardation (IUGR) newborn were selected by random sampling in 2012. And 33 cases of normal control newborn were enrolled, use high performance liquid chromatography-tandem mass spectrometry method was used to detect 4 kinds of phthalate esters (PAEs) metabolites in maternal urine: mono-n-butyl phthalate ester (MBP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and three kinds of cortisol corticosterone metabolites, tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF), tetrahydrocortisone (THE), and analyze the association between phthalate esters (PAEs) metabolites in maternal urine and 11&beta;-HSD2 enzyme activity.

RESULTSMBP, MEHP, MEHHP, MEOHP metabolites can be detected in 98% (65 cases) , 89% (59 cases), 91% (60 cases), 91% (60 cases) of all 66 maternal urine samples, respectively. The median concentrations of test material in case group were 31.20 ng/ml for MBP, 24.61 ng/ml for MEHHP, 11.72 ng/ml for MEOHP and 48.67 ng/ml for SumDEHP which were significantly higher than those of the control group (were 17.32, 12.03, 5.68 and 28.64 ng/ml); 11&beta;-HSD2 activity in case group ((THF+allo-THF)/THE = (0.79 ± 0.09) ng/ml) was significantly lower than that of the control group((THF+allo-THF)/THE = (0.58 ± 0.04) ng/ml); PAEs metabolites MBP (&beta;' = 1.12), MEHHP(&beta;' = 1.14), MEOHP(&beta;' = 1.10), SumDEHP(&beta;' = 1.08) in baby boy mother's urine was reversely correlated to 11&beta;-HSD2 activity.

CONCLUSIONSPAEs could affect fetal development by inhibit 11&beta;-HSD2 activity.

11-beta-Hydroxysteroid Dehydrogenase Type 2 ; Chromatography, Liquid ; Diethylhexyl Phthalate ; analogs & derivatives ; Fetal Development ; Humans ; Infant, Newborn ; Male ; Mass Spectrometry ; Phthalic Acids ; Tetrahydrocortisol ; analogs & derivatives ; Tetrahydrocortisone

Seven terpenoids and three sterols were isolated from the methanol extracts of the aerial parts of Ricinus communis by chromatography methods and their structures were identified by spectra analysis as ficusic acid( 1), phytol(2), callyspinol(3) , lupeol(4), 30-norlupan-3beta-ol-20-one(5) , lup-20(29)-en-3beta,15alpha-diol(6) , acetylaleuritolic acid( 7), stigmast4-en-3-one(8) , stig-mast-4-en-6beta-ol-3-one(9) , and stigmast4-en-3,6-dione(10). Compounds 1-3 and 5-10 were obtained from this species for the first time and 5 and 6 showed significant inhibitive activity and good selectivity against 11beta-HSD of mouse and human in vitro. [Key words] Ricinus communis; terpenoids; sterols; 11beta-HSD
11-beta-Hydroxysteroid Dehydrogenase Type 1 ; antagonists & inhibitors ; 11-beta-Hydroxysteroid Dehydrogenase Type 2 ; antagonists & inhibitors ; Animals ; Diabetes Mellitus ; drug therapy ; enzymology ; Humans ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Inhibitory Concentration 50 ; Mice ; Ricinus ; chemistry ; Sterols ; pharmacology ; therapeutic use ; Terpenes ; pharmacology ; therapeutic use

OBJECTIVETo investigate the mRNA and protein expressions of 11beta-Hydroxysteroid dehydrogenase type 2 (11betaHSD2) in patients with atrial fibrillation.

METHODSRight and left atrial lateral wall tissue samples were obtained during mitral/aortic valve replacement operation from 25 patients with rheumatic heart valve disease (12 in sinus rhythm and 13 in chronic atrial fibrillation). Realtime quantitative PCR and Western blot were used to determine the mRNA and protein expressions of 11betaHSD2 in atria specimens. The distribution of 11betaHSD2 in human atrial tissue was analyzed by specific immunohistochemical staining. Echocardiography examination was performed before operation.

RESULTSThe left atrial diameters were significantly higher in the atrial fibrillation group as compared to sinus rhythm group (P < 0.01). Similarly, mRNA expression of 11betaHSD2 (0.86 +/- 0.14 vs 0.33 +/- 0.12 in right atria, 0.95 +/- 0.15 vs 0.37 +/- 0.10 in left atria, all P < 0.01) and protein expression of 11betaHSD2 (1.18 +/- 0.64 vs 0.71 +/- 0.21 in right atria, P < 0.01; and 1.36 +/- 0.58 vs 0.85 +/- 0.15 in left atria, P < 0.05) were also significantly upregulated in atrial fibrillation groups than those in sinus rhythm groups. The mRNA and protein expressions of 11betaHSD2 were similar between left atria and right atria both in fibrillation and sinus groups (all P > 0.05). The special immunohistochemical staining demonstrated that 11betaHSD2 was abundant in the human atrial myocardium and located mainly in the cytoplasm.

CONCLUSIONThese findings suggested that upregulated 11betaHSD2 might be associated to the development and persistence of atrial fibrillation.

11-beta-Hydroxysteroid Dehydrogenase Type 2 ; metabolism ; Adult ; Atrial Fibrillation ; metabolism ; physiopathology ; Female ; Heart Atria ; metabolism ; physiopathology ; Humans ; Male ; Middle Aged ; Myocardium ; metabolism ; RNA, Messenger ; genetics ; Rheumatic Heart Disease ; metabolism ; physiopathology

BACKGROUND: Insulin resistance is an integral feature of metabolic syndromes, including obesity, hyperglycemia, and hyperlipidemia. In this study, we evaluated whether the aloe component could reduce obesity-induced inflammation and the occurrence of metabolic disorders such as blood glucose and insulin resistance. METHODS: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. RESULTS: Aloe QDM lowered fasting blood glucose and plasma insulin compared with HFD. Obesity-induced inflammatory cytokine (IL-1beta, -6, -12, TNF-alpha) and chemokine (CX3CL1, CCL5) mRNA and protein were decreased markedly, as was macrophage infiltration and hepatic triglycerides by Aloe QDM. At the same time, Aloe QDM decreased the mRNA and protein of PPARgamma/LXRalpha and 11beta-HSD1 both in the liver and WAT. CONCLUSION: Dietary aloe formula reduces obesity-induced glucose tolerance not only by suppressing inflammatory responses but also by inducing anti-inflammatory cytokines in the WAT and liver, both of which are important peripheral tissues affecting insulin resistance. The effect of Aloe QDM complex in the WAT and liver are related to its dual action on PPARgamma and 11beta-HSD1 expression and its use as a nutritional intervention against T2D and obesity-related inflammation is suggested.
11-beta-Hydroxysteroid Dehydrogenase Type 1 ; Aloe ; Animals ; Blood Glucose ; Blotting, Western ; Cytokines ; Diabetes Mellitus, Type 2 ; Diet ; Diet, High-Fat ; Fasting ; Glucose ; Humans ; Hyperglycemia ; Hyperlipidemias ; Inflammation ; Insulin ; Insulin Resistance ; Liver ; Macrophages ; Male ; Mice ; Mice, Obese ; Obesity ; Plasma ; PPAR gamma ; RNA, Messenger ; Thiazolidinediones ; Triglycerides