ABSTRACT
Several groups have reported the important role of estradiol (E2) and testosterone (T) in postmenopausal osteoporosis (PMOP). Because aromatase catalyzes the conversion of T to E2, the purpose of this study was to determine the influence of aromatase activity on the bone mineral density (BMD) in postmenopausal women. A total of 344 postmenopausal women were selected for this study. Serum E2, T, sex hormone-binding globulin (SHBG), calcium (Ca), alkaline phosphatase (ALP), C-terminal telopeptide of type I collagen (CTX), and procollagen type I amino-terminal propeptide (PINP) were examined. The E2/T was positively associated with total hip BMD and PINP (p<0.05). When E2/T was divided into quartiles, participants in lower quartiles of E2/T were likely to have higher PINP and lower BMD (p<0.05). The prevalence of osteoporosis significantly increased as E2/T ratio decreased. The receiver operating characteristic (ROC) curves were constructed for serum E2, free E2 index (FEI), and E2/T, to assess their diagnostic accuracy in PMOP. The overall area under the curve (AUC) were 0.83 (95% CI=0.77-0.88) for E2, 0.87 (95% CI=0.82-0.92) for FEI, and 0.89 (95% CI=0.85-0.94), respectively. In conclusion, the study suggests that in postmenopausal women, aromatase activity could be an important determinant of skeletal health. The women with lower aromatase activity may have greater likelihood of PMOP and the E2/T was expected to be a valuable indicator for the prediction of PMOP and to monitor the process of osteoporosis.
Subject(s)
Aromatase/metabolism , Asian People , Bone Density , Estradiol/metabolism , Hip/physiopathology , Osteoporosis, Postmenopausal/metabolism , Osteoporosis, Postmenopausal/physiopathology , Sex Hormone-Binding Globulin/metabolism , Aged , Biomarkers/metabolism , Bone Diseases, Metabolic/epidemiology , Bone Remodeling , Female , Humans , Likelihood Functions , Linear Models , Middle Aged , Osteoporosis, Postmenopausal/epidemiology , Postmenopause , Prevalence , ROC CurveABSTRACT
OBJECTIVE: To investigate the effect of pioglitazone on high-fat (HF)-diet-induced left ventricular (LV) hypertrophy and dysfunction in rats. METHODS: A total of 36 male Sprague-Dawley rats were randomly divided into 3 groups, namely, control, HF diet, and pioglitazone treatment group. High-fat diet group (HF group) animals were treated with HF diet for 30 weeks, whereas pioglitazone group was treated with HF diet for 30 weeks and pioglitazone in the last 6 weeks of the 30-week treatment. Fasting plasma free fatty acids (FFAs), serum, and myocardial triglyceride were measured. Left ventricular function was assessed by echocardiography. Renin, angiotensin II, and angiotensin types 1 and 2 (AT1/AT2) receptors in the myocardium were analyzed by immunohistochemistry and real-time polymerase chain reaction (PCR). RESULTS: Systolic blood pressure, plasma FFA, serum, and myocardial triglyceride concentrations in HF group were higher than in control and pioglitazone groups (P < .01). There was no significant difference in LV weight index and LV posterior wall thickness between HF and pioglitazone groups; both were higher than in the control group (P < .01). Left ventricular ejection fraction, fraction of shortening, and cardiac index in HF group were lower than in the control and pioglitazone groups (P < .05). Myocardial expression of angiotensin II and AT1 receptor protein in HF group was higher when compared with the control and pioglitazone groups (P < .01). Myocardial renin and angiotensin II messenger RNA (mRNA) in HF group was also higher when compared with the control and pioglitazone groups, whereas the expression of AT2 mRNA was lower (P < .01). CONCLUSION: Pioglitazone diminished HF-diet-induced LV dysfunction. These effects may be related to a reduction in blood pressure, myocardial triglycerides sedimentary, and suppression of renin-angiotensin system.
Subject(s)
Diet, High-Fat/adverse effects , Thiazolidinediones/pharmacology , Ventricular Dysfunction, Left/drug therapy , Ventricular Remodeling/drug effects , Animals , Blood Pressure/drug effects , Echocardiography , Fatty Acids, Nonesterified/metabolism , Hypertrophy, Left Ventricular/drug therapy , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/physiopathology , Hypoglycemic Agents/pharmacology , Male , Myocardium/metabolism , Myocardium/pathology , Pioglitazone , Random Allocation , Rats , Rats, Sprague-Dawley , Renin-Angiotensin System/drug effects , Triglycerides/metabolism , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathologyABSTRACT
BACKGROUND AND AIMS: Animal experiments showed that interaction between advanced glycation end products (AGE) and their receptors (RAGE) play an important role in the pathogenesis of diabetic complications. Soluble RAGE (sRAGE) can function as a decoy for RAGE ligands. The present study aimed to examine the levels of AGEs, RAGE and sRAGE in patients with type 2 diabetes (T2D). METHODS: RAGE gene expression was determined by real-time PCR in 50 patients with T2D (27 men, mean age 52 ± 7.7 years) and 50 age-matched controls without T2D. Serum AGEs and sRAGEs were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum level of AGEs was increased in patients with T2D (10.35 ± 2.27 µg/mL vs.7.69 ± 0.56 µg/mL, p <0.05). sRAGE was decreased in patients with T2D (573.6 ± 172.5 pg/mL vs. 603.4 ± 120.8 pg/mL p <0.01). RAGE gene expression was higher in T2D than in controls (p <0.01). There was an association between monocyte RAGE and serum levels of AGEs in both T2D patients (r = 0.29, p = 0.03) and controls (r = 0.31, p = 0.02). Serum AGEs correlated with homeostasis model assessment of insulin resistance (HOMA-IR) in both patients with T2D (r = 0.322, p = 0.004) and controls (r = 0.281, p = 0.003). CONCLUSIONS: Serum AGEs and monocyte RAGE expression are increased in patients with T2D, whereas serum sRAGE is decreased. Pharmacological intervention on serum AGEs and sRAGE may be a potential therapy for diabetes.
