Effect of Hyperprolactinemia on Bone Metabolism: Focusing on Osteopenia/Osteoporosis.

Prolactin is a hormone secreted from lactotroph cells in the anterior pituitary gland to induce lactation after birth. Hyperprolactinemia unrelated to lactation is a common cause of amenorrhea in women of a childbearing age, and a consequent decrease in the gonadotropin-releasing hormone (GnRH) by a high prolactin level can result in decreased bone mineral density. Osteoporosis is a common skeletal disorder characterized by decreased bone mineral density (BMD) and quality, which results in decreased bone strength. In patients with hyperprolactinemia, changes in BMD can be induced indirectly by the inhibition of the GnRH-gonadal axis due to increased prolactin levels or by the direct action of prolactin on osteoblasts and, possibly, osteoclast cells. This review highlights the recent work on bone remodeling and discusses our knowledge of how prolactin modulates these interactions, with a brief literature review on the relationship between prolactin and bone metabolism and suggestions for new possibilities.

Pancreatic fat accumulation is associated with decreased ß-cell function and deterioration in glucose tolerance in Korean adults.

AIMS: This study was designed to investigate the association between pancreatic fat content (PFC) and insulin secretory capacity as well as glucose tolerance in Korean adults. MATERIALS: A total of 39 participants (mean age 49.9 years, 53% males) without a previous history of diabetes, or those previously diagnosed as having diabetes but with less than 10 years of disease duration and no medication history were included. They were stratified according to the results of the oral glucose tolerance test (OGTT): normal glucose tolerance, prediabetes, and diabetes. METHODS: All participants underwent the proton magnetic resonance spectroscopy (1 H-MRS) to assess PFC. Insulin sensitivity and ß-cell function were measured by the frequently sampled intravenous glucose tolerance tests (FSIVGTT) and OGTT-derived indices. RESULTS: As glucose tolerance deteriorated, parameters such as Stumvoll index, oral glucose insulin sensitivity index, homeostatic model assessment (HOMA)-ß, insulinogenic index and oral disposition index from the OGTT, and acute insulin response to glucose (AIR) and disposition index (DI) from the FSIVGTT were decreased. PFC increased with deterioration in glucose tolerance (NGT: 12.0%, prediabetes: 23.7%, and diabetes: 31.9%). Correlation analysis indicated that glucose levels at 60 and 120 min during the OGTT were positively correlated with PFC. Also, there was a significant negative correlation between PFC and DI as well as AIR derived from the FSIVGTT. CONCLUSIONS: PFC evaluated by 1 H-MRS in Korean adults was higher in those diagnosed with diabetes than those with normal glucose tolerance status. PFC also showed a significant negative correlation with indices reflecting beta cell function.

Descriptive Epidemiology and Survival Analysis of Acromegaly in Korea.

BACKGROUND: Acromegaly is a rare, slowly progressive disease. Its mechanism is not fully understood, and epidemiological research on Korean patients with acromegaly is scarce. The purpose of this study was to determine the incidence and prevalence of acromegaly and assess the comorbidities and survival benefits based on treatment options. METHODS: This nationwide population-based cohort study was conducted using data of the Korean Health Insurance Review and Assessment claims database to evaluate the incidence of newly diagnosed acromegaly cases during 2013-2017. RESULTS: During the 5-year period, 1,093 patients were newly diagnosed with acromegaly. The average annual incidence was 4.2 cases per million per year, and the prevalence was 32.1 cases per million during this period. The incidence of hypertension was low after medical treatment (hazard ratio, 0.257; 95% confidence interval, 0.082-0.808; P = 0.020), but the incidence of diabetes showed no significant difference across treatment modalities. Over a period of 6 years since diagnosis, we found that patients treated for acromegaly had a significantly higher survival rate than those untreated (P < 0.001). CONCLUSION: The annual incidence rate of Korean patients with acromegaly was similar to that reported in previous studies. Using nationwide population data, our study emphasized the importance of treatment in acromegaly patients.

Spironolactone Attenuates Methylglyoxal-induced Cellular Dysfunction in MC3T3-E1 Osteoblastic Cells.

BACKGROUND: Methylglyoxal (MG) is associated with the pathogenesis of age- and diabetes-related complications. Spironolactone is a competitive antagonist of aldosterone that is widely employed in the treatment of hypertension and heart failure. This study examined the effects of spironolactone on MG-induced cellular dysfunction in MC3T3-E1 osteoblastic cells. METHODS: MC3T3-E1 cells were treated with spironolactone in the presence of MG. The mitochondrial function, bone formation activity, oxidative damage, inflammatory cytokines, glyoxalase I activity, and glutathione (GSH) were measured. RESULTS: Pretreatment of MC3T3-E1 osteoblastic cells with spironolactone prevented MG-induced cell death, and improved bone formation activity. Spironolactone reduced MG-induced endoplasmic reticulum stress, production of intracellular reactive oxygen species, mitochondrial superoxides, cardiolipin peroxidation, and inflammatory cytokines. Pretreatment with spironolactone also increased the level of reduced GSH and the activity of glyoxalase I. MG induced mitochondrial dysfunction, but markers of mitochondrial biogenesis such as mitochondrial membrane potential, adenosine triphosphate, proliferator-activated receptor gamma coactivator 1α, and nitric oxide were significantly improved by treatment of spironolactone. CONCLUSION: Spironolactone could prevent MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells by reduction of oxidative stress. The oxidative stress reduction was explained by spironolactone's inhibition of advanced glycation end-product formation, restoring mitochondrial dysfunction, and anti-inflammatory effect.

Oleuropein attenuates the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-perturbing effects on pancreatic ß-cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disrupting compound and persistent organic pollutant that has been associated with diabetes in several epidemiological studies. Oleuropein, a major phenolic compound in olive fruit, is a superior antioxidant and radical scavenger. This study aimed to examine the effects of oleuropein against TCDD-induced stress response in a pancreatic beta cell line, INS-1 cells. Cells were pre-incubated with various concentrations of oleuropein and then stimulated with TCDD (10 nM) for 48 hrs. When treated with TCDD, INS-1 cells produced robust amounts of prostaglandin E2 (PGE2) compared to the untreated control, and this increase was inhibited by oleuropein treatment. TCDD increased Ca2+-independent phospholipase A2 (iPLA2ß) level, but had no effect on Group 10 secretory phospholipase A2 (PLA2G10) level, while oleuropein deceased the levels of iPLA2ß and PLA2G10 in the presence of TCDD. Cyclooxygenase-1 (COX-1) was significantly increased by TCDD treatment and attenuated with oleuropein pretreatment. Oleuropein decreased TCDD-mediated production of JNK, TNF-α, and ROS. In addition, oleuropein increased Akt and GLUT2 levels suppressed by TCDD in INS-1 cells. Thus, the results suggest that oleuropein prevents pancreatic beta cell impairment by TCDD.

Catalpol protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytotoxicity in osteoblastic MC3T3-E1 cells.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental contaminant that produces a wide variety of adverse effects in humans. Catalpol, a major bioactive compound enriched in the dried root of Rehmannia glutinosa, is a major iridoid glycoside that alleviates bone loss. However, the detailed mechanisms underlying the effects of catalpol remain unclear. The present study evaluated the effects of catalpol on TCDD-induced cytotoxicity in osteoblastic MC3T3-E1 cells. Catalpol inhibited TCDD-induced reduction in cell viability and increases in apoptosis and autophagic activity in osteoblastic MC3T3-E1 cells. Additionally, pretreatment with catalpol significantly decreased the nitric oxide and nitrite levels compared with a control in TCDD-treated cells and significantly inhibited TCDD-induced increases in the levels of cytochrome P450 1A1 and extracellular signal-regulated kinase. Pretreatment with catalpol also effectively restored the expression of superoxide dismutase and extracellular signal-regulated kinase 1 and significantly enhanced the expression of glutathione peroxidase 4 and osteoblast differentiation markers, including alkaline phosphatase and osterix. Taken together, these findings demonstrate that catalpol has preventive effects against TCDD-induced damage in MC3T3-E1 osteoblastic cells.

Tetrabromobisphenol A Promotes the Osteoclastogenesis of RAW264.7 Cells Induced by Receptor Activator of NF-kappa B Ligand In Vitro.

BACKGROUND: Tetrabromobisphenol A (TBBPA), one of the most widely used brominated flame-retardants, is a representative persistent organic pollutants group. Studies on TBBPA toxicity have been conducted using various target cells; however, few studies have investigated TBBPA toxicity in bone cells. Therefore, this study investigated the in vitro effects of TBBPA on osteoclasts, a cell type involved in bone metabolism. METHODS: RAW264.7 cells were cultured in medium containing 50 ng/mL receptor activator of nuclear factor kappa B ligand (RANKL) and varying concentrations of TBBPA. To evaluate the effects of TBBPA on the differentiation and function of osteoclasts, osteoclast-specific gene expression, tartrate-resistant acid phosphatase (TRAP) activity, bone resorbing activity, mitochondrial membrane potential (MMP) and mitochondrial superoxide were measured. RESULTS: The presence of 20 µ TBBPA significantly increased TRAP activity in RANKL-stimulated RAW264.7 cells, the bone resorbing activity of osteoclasts, and the gene expression of Akt2, nuclear factor of activated T-cells cytoplasmic 1, and chloride channel voltage-sensitive 7. However, TBBPA treatment caused no change in the expression of carbonic anhydrase II, cathepsin K, osteopetrosis-associated transmembrane protein 1, Src, extracellular signal-related kinase, GAB2, c-Fos, or matrix metalloproteinase 9. Furthermore, 20 µ TBBPA caused a significant decrease in MMP and a significant increase in mitochondrial superoxide production. CONCLUSION: This study suggests that TBBPA promotes osteoclast differentiation and activity. The mechanism of TBBPA-stimulated osteoclastogenesis might include increased expression of several genes involved in osteoclast differentiation and reactive oxygen species production.

Biochanin A prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced adipocyte dysfunction in cultured 3T3-L1 cells.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant. TCDD accumulates in the food chain, mainly in the fatty tissues of the human body where it causes various toxic effects. Biochanin A is a natural organic compound in the class of phytochemicals known as flavonoids. We investigated whether biochanin A suppresses TCDD-induced loss of adipogenic action using 3T3-L1 adipocytes as a cell culture model of wasting syndrome. In the present study, biochanin A suppressed TCDD-induced loss of lipid accumulation. Pretreating the cells with biochanin A increased the levels of the adipogenesis-associated factors peroxisome proliferator-activated receptor γ and adiponectin, which were inhibited by TCDD. TCDD decreased insulin-stimulated glucose uptake, which was effectively restored by pretreatment with biochanin A. Biochanin A also inhibited the TCDD-driven decrease in production of insulin receptor substrate-1 and glucose transporter 4. These results suggest a preventive effect of biochanin A against TCDD in the development of insulin resistance and diabetes. TCDD increased production of intracellular calcium ([Ca2+]i), prostaglandin E2, cytosolic phospholipase A2, and cyclooxygenase-1, while reducing the level of peroxisome proliferator-activated receptor gamma coactivator 1-alpha. However, biochanin A inhibited these TCDD-induced effects. We conclude that biochanin A is an attractive compound for preventing TCDD-induced wasting syndrome.

Xanthohumol ameliorates 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cellular toxicity in cultured MC3T3-E1 osteoblastic cells.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant. Xanthohumol is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The aim of the current study was to explore the role of xanthohumol in modulating the toxicity of TCDD in MC3T3-E1 osteoblastic cells. In cells treated with TCDD alone, intracellular Ca2+ concentrations, mitochondrial membrane potential disruption, reactive oxygen species production, cardiolipin peroxidation, nitric oxide release and cytochrome P450 1A1 expression were significantly increased. TCDD treatment increased the mRNA levels of extracellular signal-regulated kinase 1 and nuclear factor kappa B, and significantly decreased the level of protein kinase B (AKT) in MC3T3-E1 osteoblastic cells. However, the presence of xanthohumol alleviated the pathological effects of TCDD. In addition, xanthohumol treatment significantly increased the expression of genes associated with osteoblast differentiation (alkaline phosphatase, osteocalcin, osteoprotegerin and osterix). We conclude that xanthohumol has a beneficial influence and may antagonize TCDD toxicity in osteoblastic cells.

Glabridin attenuates antiadipogenic activity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in murine 3T3-L1 adipocytes.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has various toxicological effects in adipose tissue. Evidence is accumulating that glabridin, a flavonoid extracted from licorice, has beneficial effects on the regulation of glucose homeostasis. In this study, we investigated whether glabridin suppresses TCDD-induced loss of adipogenic action using 3T3-L1 adipocytes as a cell culture model of wasting syndrome. Glabridin effectively suppressed TCDD-induced loss of lipid accumulation in this model. Pretreating cells with glabridin increased the gene expression of not only the adipogenesis-associated key transcription factors peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha, but also lipoprotein lipase in the presence of TCDD. TCDD decreased insulin-stimulated glucose uptake, which was effectively restored by pretreatment with glabridin. Glabridin also inhibited the TCDD-driven decreased production of insulin receptor substrate 1 and glucose transporter 4. TCDD increased the production of mitochondrial superoxides, prostaglandin E2 , phospholipase A2 , cyclooxygenase-1 and intracellular calcium concentrations, while reducing the production of PPARγ coactivator 1 alpha and glycolysis. However, glabridin treatment reduced these TCDD-induced effects. We conclude that glabridin suppresses the TCDD-induced loss of lipid accumulation in 3T3-L1 adipocytes by regulating the levels of PPARγ, CCAAT/enhancer binding protein alpha, lipoprotein lipase, glucose uptake, prostaglandin E2 and energy metabolism. These results also provide in vitro evidence of the effects of glabridin on adipocyte metabolism, which suggests a protective effect against dioxin exposure in the development of insulin resistance and diabetes.

27-Deoxyactein prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cellular damage in MC3T3-E1 osteoblastic cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental contaminant that exerts its toxicity through a variety of signaling mechanisms. The present study evaluated the effects of 27-deoxyactein, one of the major constituents isolated from Cimicifuga racemosa, on TCDD-induced toxicity in osteoblastic MC3T3-E1 cells. TCDD reduced cell survival, markedly increased apoptosis, and enhanced autophagy activity. However, pre-treatment with 27-deoxyactein attenuated all TCDD-induced effects and significantly decreased intracellular calcium (Ca2+) concentrations, the collapse of the mitochondrial membrane potential (MMP), the level of reactive oxygen species (ROS), and cardiolipin peroxidation compared to the TCDD-treated controls. Additionally, TCDD-induced increases in the levels of aryl hydrocarbon receptor (AhR), cytochrome P450 1A1 (CYP1A1), and extracellular signal-regulated kinase (ERK) were significantly inhibited by 27-deoxyactein. The mRNA levels of superoxide dismutase (SOD), ERK1, and nuclear factor kappa B (NF-κB) were also effectively restored by pre-treatment with 27-deoxyactein. Furthermore, 27-deoxyactein significantly increased the expressions of genes associated with osteoblast differentiation, including alkaline phosphatase (ALP), osteocalcin, bone sialoprotein (BSP), and osterix. Taken together, the present findings demonstrate the preventive effects of 27-deoxyactein on TCDD-induced damage in osteoblasts.

Actein alleviates 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated cellular dysfunction in osteoblastic MC3T3-E1 cells.

The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to affect bone metabolism. We evaluated the protective effects of the triterpene glycoside actein from the herb black cohosh against TCDD-induced toxicity in MC3T3-E1 osteoblastic cells. We found that TCDD significantly reduced cell viability and increased apoptosis and autophagy in MC3T3-E1 osteoblastic cells (P < .05). In addition, TCDD treatment resulted in a significant increase in intracellular calcium concentration, mitochondrial membrane potential collapse, reactive oxygen species (ROS) production, and cardiolipin peroxidation, whereas pretreatment with actein significantly mitigated these effects (P < .05). The effects of TCDD on extracellular signal-related kinase (ERK), aryl hydrocarbon receptor, aryl hydrocarbon receptor repressor, and cytochrome P450 1A1 levels in MC3T3-E1 cells were significantly inhibited by actein. The levels of superoxide dismutase, ERK1, and nuclear factor kappa B mRNA were also effectively restored by pretreatment with actein. Furthermore, actein treatment resulted in a significant increase in alkaline phosphatase (ALP) activity and collagen content, as well as in the expression of genes associated with osteoblastic differentiation (ALP, type I collagen, osteoprotegerin, bone sialoprotein, and osterix). This study demonstrates the underlying molecular mechanisms of cytoprotection exerted by actein against TCDD-induced oxidative stress and osteoblast damage.

Blood lead is significantly associated with metabolic syndrome in Korean adults: an analysis based on the Korea National Health and Nutrition Examination Survey (KNHANES), 2008.

BACKGROUND: Although an association between low-level environmental heavy metal exposure and the incidence of metabolic syndrome (MS) has been hypothesized, little research on this topic has been conducted on a population-wide level. METHODS: We analyzed MS status and whole blood lead, mercury, cadmium, manganese, and creatinine-adjusted urine arsenic concentrations in 1,405 subjects, ≥ 20 years of age, who were registered for the Korea National Health and Nutrition Examination Survey, 2008. RESULTS: Various demographic and biochemical parameters were associated with MS and blood heavy metal status. After adjusting for these variables, lead was the only heavy metal that was significantly associated with MS. Lead concentrations in subjects with MS were significantly higher than those in subjects without MS (p = 0.015). The prevalence of MS and a moderate/high risk for cardiovascular disease, as determined by Framingham risk score, also increased significantly according to the logarithmic transformation of the lead quartile (p < 0.001). The odds ratios and 95% confidence intervals for MS were 1.56 (0.90-2.71), 1.63 (0.94-2.83), and 2.57 (1.46-4.51) for the second, third, and fourth quartiles of the log-transformed lead quartile, respectively, as compared with those of the lowest quartile after multiple adjustments for confounding factors. Serum triglyceride level was the only MS diagnostic component significantly associated with lead level in a multiple linear regression analysis (p = 0.006). CONCLUSIONS: These findings suggest that a higher prevalence of MS is associated with higher blood lead levels in the Korean population.

Change in somatostatinergic tone of acromegalic patients according to the size of growth hormone-producing pituitary tumors.

The aim of this study was to investigate the relationship between somatostatinergic tone (SST) and the size of growth hormone (GH)-producing pituitary tumors. GH levels of 29 patients with newly diagnosed acromegaly were measured using a 75-gram oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), and an octreotide suppression test (OST). Differences between GH levels during the ITT and the OGTT (ΔGHIO), and between the OGTT and the OST at the same time point (ΔGHOS) were compared according to the size of the tumor and the response pattern to the OST. ΔGHIO of macroadenomas (n=22) was non-significantly higher than those of microadenomas while ΔGHOS of macroadenomas were significantly higher than those of microadenomas. According to further analyses of macroadenomas based on the response pattern to the OST, GH levels during the ITT were significantly higher in non-responders. ΔGHOS showed near-significant differences between responders and non-responders. In conclusion, as the size of the pituitary tumor increases, the effect of glucose on SST appears to be attenuated. Macroadenomas that are non-responders to the OST possess a portion of GH secretion exceeding the range of regulation by SST.

Arsenic exposure and prevalence of diabetes mellitus in Korean adults.

It has been suggested that there is an association between environmental, low-level arsenic exposure and the risk of diabetes mellitus (DM), but little research has been conducted. Here, the glucose tolerance status and urinary creatinine adjusted total arsenic concentrations were analyzed in 3,602 subjects ≥ 20 yr of age who were registered for the Korea National Health and Nutrition Examination Survey, 2008-2009. Various demographic parameters were associated with urinary arsenic concentrations. After adjusting for these variables, urinary arsenic concentrations in subjects with DM were significantly higher than those in subjects with normal glucose tolerance and those with impaired fasting glucose (P < 0.001). Compared with the lowest quartile ( < 70.7 µg/g creatinine), the odds ratios and 95% confidence intervals for DM were 1.11 (0.73-1.68), 1.42 (0.94-2.13), and 1.56 (1.03-2.36) for urinary arsenic concentrations of 70.7 to < 117.7, 117.7 to < 193.4, and ≥ 193.4 µg/g creatinine, respectively, following multivariate adjustment. Furthermore, the urinary total arsenic concentration was inversely associated with the insulin secretion index, HOMA2 %B (ß = -0.033, P = 0.032). These findings suggest that arsenic exposure, possibly involving beta cell dysfunction, is associated with an increased risk of DM in the Korean population.

Trends in the Prevalence of Obesity and Its Phenotypes Based on the Korea National Health and Nutrition Examination Survey from 2007 to 2017 in Korea.

This study used data from the Korea National Health and Nutrition Examination Survey IV-VII from 2007 to identify the prevalence of obesity and its phenotypes (metabolically unhealthy obesity [MUO] and metabolically healthy obesity [MHO]) and their secular changes. The prevalence of obesity in Korea increased with significant secular changes observed (ß=0.326, P trend <0.01) between 2007 and 2017, and especially in men (ß=0.682, P trend <0.001) but not in women. The changes in the prevalence of obesity during the study period were different between men and women (P=0.001). The prevalence of MUO significantly increased only in men (ß=0.565, P trend <0.01), while that of MHO increased only in women (ß=0.179, P<0.05), especially in the younger age group (ß=0.308, P<0.01).

Efficacy of risedronate with cholecalciferol on 25-hydroxyvitamin D level and bone turnover in Korean patients with osteoporosis.

BACKGROUND: We performed a randomized, double-blind, prospective, 16-week clinical trial to evaluate the efficacy and safety of risedronate with and without cholecalciferol on 25-hydroxyvitamin D [25(OH)D] levels and bone markers in Korean patients with osteoporosis. METHODS: We randomly assigned 164 adults with osteoporosis to one of two treatment groups: weekly risedronate 35 mg and cholecalciferol 5600 IU combined in a single pill (RSD+) or weekly risedronate 35 mg alone (RSD). We measured serum levels of 25(OH)D, parathyroid hormone (PTH), and bone markers and performed muscle function tests, at baseline and after 16 weeks of treatment. RESULTS: After 16 weeks of treatment, mean serum 25(OH)D increased significantly from 39·8 to 70·8 nmol/l in the RSD+ group and declined significantly from 40·5 to 35 nmol/l in the RSD group. Although both treatment groups had significant increases in serum PTH over baseline during the study, the RSD group had a significantly larger increase than the RSD+ group (13·6 vs 4·8 ng/l; P = 0·0005). In both groups, serum bone-specific alkaline phosphatase (BSAP) and C-terminal telopeptide (CTX) declined rapidly; there were no significant differences between groups. There was also no significant difference between groups in lower-extremity function tests. The overall incidence of clinical adverse events was not significantly different between groups. CONCLUSION: In patients with osteoporosis, a once-weekly pill of risedronate and cholecalciferol provided equivalent antiresorptive efficacy to risedronate alone in terms of bone turnover and improved 25(OH)D level over a 16-week treatment period without significant adverse events.

Descriptive Epidemiology and Survival Analysis of Prolactinomas and Cushing's Disease in Korea.

BACKGROUND: Only a few studies have established the epidemiology of prolactinoma and Cushing's disease in Korea. Furthermore, the incidence of these disease are increasing than before associated with the development of technologies. This study was designed to evaluate the epidemiology of prolactinoma and Cushing's disease and their survival analysis according to treatment. METHODS: The nationwide, population-based study evaluated incidence and prevalence of prolactinoma and Cushing's disease using de-identified claims data in The Korean Health Insurance Review and Assessment Service database between 2013 and 2017. The survival analysis investigated regarding treatment over a period of 6 years. A log-rank test and Cox proportional hazard regression analysis were used. RESULTS: The 6,056 patients with newly diagnosed prolactinoma and 584 patients with Cushing's disease were recorded between 2013 and 2017. The annual incidence of prolactinoma was 23.5 cases per million, and its prevalence was 82.5 cases per million, and 2.3 cases per million/year and 9.8 cases per million for Cushing's disease. The survival benefit was insignificant in prolactinoma according to treatment, but treatment of Cushing's disease ameliorated the survival rate significantly. CONCLUSION: Overall, the incidence of prolactinoma and Cushing's disease was similar with those found previously, but the prevalence of two diseases were inconsistent when compared with the early studies. The present study also proposed necessity of treatment in Cushing's disease for improving the survival rate.

Epidemiology of Functioning Pituitary Adenomas.

Pituitary adenomas (PAs) are defined as benign monoclonal tumors in the pituitary gland that cause symptoms due to either hormonal hypersecretion or a space-occupying effect, and are classified as functioning or non-functioning. Because of their rarity and slow-growing with symptomless nature in most cases, it has been challenging to investigate the epidemiology of PAs. Considering their public health impact and association with increased morbidity and mortality, however, it is essential to understand the prevalence and incidence of PAs in order to improve patient outcomes and to minimize the resultant burden on the health care system. Fortunately, developments in imaging modalities and easier access to large-scale population data have enabled investigators to analyze the epidemiology of PAs more accurately. This review summarizes previously reported epidemiologic data on functioning PAs in Korea and other countries.

Orientin reduces the inhibitory effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on adipogenic differentiation and insulin signaling pathway in murine 3T3-L1 adipocytes.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) accumulates in human body, probably influencing adipocyte differentiation and causing various toxic effects, including wasting syndrome. Recently, orientin, a phenolic compound abundant in natural health products, has been shown to have antioxidant properties. We investigated the protective effects of orientin against TCDD-induced adipocyte dysfunction and its underlying mechanisms. In this study, orientin suppressed TCDD-induced loss of lipid accumulation. Orientin inhibited TCDD-driven decreases in the levels of peroxisome proliferator-activated receptor γ and adiponectin. Orientin also reduced TCDD-induced prostaglandin E2, and cytosolic phospholipase A2α levels, and increased TCDD-inhibited peroxisome proliferator-activated receptor gamma coactivator 1-alpha levels in 3T3-L1 adipocytes. TCDD reduced the levels of insulin receptor substrate 1 and glucose transporter 4, and decreased insulin-stimulated glucose uptake activity; however, orientin diminished these TCDD-induced effects. These results suggest that orientin may have beneficial effects on the prevention of TCDD-induced wasting syndrome and type II diabetes mellitus accompanied by insulin resistance.