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

Adipose tissue inflammation is considered a major contributing factor in the development of obesity-associated insulin resistance and cardiovascular diseases. However, the cause of adipose tissue inflammation is presently unclear. The role of mitochondria in white adipocytes has long been neglected because of their low abundance. However, recent evidence suggests that mitochondria are essential for maintaining metabolic homeostasis in white adipocytes. In a series of recent studies, we found that mitochondrial function in white adipocytes is essential to the synthesis of adiponectin, which is the most abundant adipokine synthesized from adipocytes, with many favorable effects on metabolism, including improvement of insulin sensitivity and reduction of atherosclerotic processes and systemic inflammation. From these results, we propose a new hypothesis that mitochondrial dysfunction in adipocytes is a primary cause of adipose tissue inflammation and compared this hypothesis with a prevailing concept that “adipose tissue hypoxia” may underlie adipose tissue dysfunction in obesity. Recent studies have emphasized the role of the mitochondrial quality control mechanism in maintaining mitochondrial function. Future studies are warranted to test whether an inadequate mitochondrial quality control mechanism is responsible for mitochondrial dysfunction in adipocytes and adipose tissue inflammation.
11-beta-Hydroxysteroid Dehydrogenases ; Adipocytes ; Adipocytes, White ; Adipokines ; Adiponectin ; Adipose Tissue ; Anoxia ; Cardiovascular Diseases ; Homeostasis ; Inflammation ; Insulin Resistance ; Metabolism ; Mitochondria ; Nitric Oxide ; Obesity ; Quality Control

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

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 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

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

The hypothalamus plays a key role in the regulation of body weight by balancing the intake of food, energy expenditure, and body fat stores, as evidenced by the fact that most monogenic syndromes of morbid obesity result from mutations in genes expressed in the hypothalamus. Hypothalamic obesity is a result of impairment in the hypothalamic regulatory centers of body weight and energy expenditure, and is caused by structural damage to the hypothalamus, radiotherapy, Prader-Willi syndrome, and mutations in the LEP, LEPR, POMC, MC4R and CART genes. The pathophysiology includes loss of sensitivity to afferent peripheral humoral signals, such as leptin, dysregulated insulin secretion, and impaired activity of the sympathetic nervous system. Dysregulation of 11beta-hydroxysteroid dehydrogenase 1 activity and melatonin may also have a role in the development of hypothalamic obesity. Intervention of this complex entity requires simultaneous targeting of several mechanisms that are deranged in patients with hypothalamic obesity. Despite a great deal of theoretical understanding, effective treatment for hypothalamic obesity has not yet been developed. Therefore, understanding the mechanisms that control food intake and energy homeostasis and pathophysiology of hypothalamic obesity can be the cornerstone of the development of new treatments options. Early identification of patients at-risk can relieve the severity of weight gain by the provision of dietary and behavioral modification, and antiobesity medication. This review summarizes recent advances of the pathophysiology, endocrine characteristics, and treatment strategies of hypothalamic obesity.
11-beta-Hydroxysteroid Dehydrogenases ; Adipose Tissue ; Adolescent* ; Body Weight ; Child* ; Eating ; Energy Metabolism ; Homeostasis ; Humans ; Hypothalamus ; Insulin ; Leptin ; Melatonin ; Obesity* ; Obesity, Morbid ; Prader-Willi Syndrome ; Pro-Opiomelanocortin ; Radiotherapy ; Sympathetic Nervous System ; Weight Gain

Glycyrrhizic acid is a component of licorice. It can cause hypokalemia through the inhibition of 11beta-hydroxysteroid dehydrogenase. The severity of symptoms depends on the dose and duration of licorice intake, as well as the individual susceptibility. The safe dose of licorice is 10 mg per day. Even a small amount of licorice can cause side effects, including hypokalemia in patients taking diuretics, with diarrhea, or congestive heart failure. We experienced a 59-year-old male with muscle weakness. He had ingested losartan and indapamide due to hypertension. At presentation, he had ingested 8 mg of licorice daily for the previous 17 days. The patient presented with severe hypokalemia (1.8 mEq/L) and rhabdomyolysis. His renin activity was 0.44 ng/mL/h, and his aldosterone level was 6.0 pg/mL. After cessation of licorice and indapamide, his potassium level recovered. In conclusion, even a small amount of licorice can induce hypokalemia in patients who are taking diuretics.
11-beta-Hydroxysteroid Dehydrogenases ; Aldosterone ; Diarrhea ; Diuretics ; Glycyrrhiza ; Glycyrrhizic Acid ; Heart Failure ; Humans ; Hypertension ; Hypokalemia ; Indapamide ; Losartan ; Male ; Middle Aged ; Muscle Weakness ; Potassium ; Renin ; Rhabdomyolysis

INTRODUCTIONGlucocorticoids cause osteoporosis by decreasing bone formation and increasing bone resorption activity. Glucocorticoid action in bones depends on the activity of 11-beta-hydroxysteroid dehydrogenase type 1 (11&beta;-HSD1) enzyme, which plays an important role in regulating corticosteroids. 11&beta;-HSD1 is expressed by human and rat osteoblasts. We aimed to investigate the relationship between 11&beta;-HSD1 dehydrogenase activity and bone histomorphometric changes in glucocorticoid-induced osteoporotic bone in rats.

METHODSA total of 30 male Sprague-Dawley rats (aged three months, weighing 200-250 g) were divided into three groups of ten each. Group 1 rats were the baseline control, which were sacrificed untreated at the beginning of the study. Group 2 rats underwent sham operation and were administered with vehicle olive oil intramuscularly at 0.05 ml/kg. Group 3 rats were adrenalectomised and administered with an intramuscular injection of dexamethasone 120 μg/kg body weight/day. The treatment was started two weeks after the operation, for a duration of two months. Plasma osteocalcin, plasma pyrodinoline, plasma corticosterone and 11&beta;-HSD1 were measured, and bone histomorphometry analysis was performed.

RESULTSDexamethasone treatment caused an increase in plasma corticosterone level, together with a significant reduction in 11&beta;-HSD1 dehydrogenase activity of the bone, along with a higher plasma level of the bone resorption marker, pyridinoline. Dexamethasone treatment also caused a reduction in trabecular volume, number and thickness, and an increase in trabecular separation.

CONCLUSIONLong-term glucocorticoid treatment reduces the 11&beta;-HSD1 dehydrogenase activity in the bone, which can otherwise lead to bone loss due to the increased level of active glucocorticoids.

11-beta-Hydroxysteroid Dehydrogenase Type 1 ; metabolism ; Adrenal Cortex Hormones ; metabolism ; Amino Acids ; pharmacology ; Animals ; Body Weight ; Bone and Bones ; metabolism ; Corticosterone ; blood ; Dexamethasone ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; methods ; Gene Expression Regulation, Enzymologic ; Glucocorticoids ; metabolism ; Humans ; Male ; Osteoporosis ; metabolism ; Rats ; Rats, Sprague-Dawley