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PubMed: 0013-7227
THE HOMEODOMAIN-INTERACTING PROTEIN KINASE 2 (HIPK2) REGULATES IPF1/PDX1 TRANSCRIPTIONAL ACTIVITY.
Boucher MJ, Simoneau M, Edlund H Related Articles THE HOMEODOMAIN-INTERACTING PROTEIN KINASE 2 (HIPK2) REGULATES IPF1/PDX1 TRANSCRIPTIONAL ACTIVITY. Endocrinology. 2008 Sep 4; Authors: Boucher MJ, Simoneau M, Edlund H The homeodomain transcription factor IPF1/PDX1 plays a crucial role in both pancreas development and maintenance of beta-cell function. Targeted disruption of the Ipf1/Pdx1 gene in beta-cells of mice leads to overt diabetes and reduced Ipf1/Pdx1 gene expression results in decreased insulin expression and secretion. In humans, mutations in the IPF1 gene have been linked to diabetes. Hence, the identification of molecular mechanisms regulating the transcriptional activity of this key transcription factor is of great interest. Herein, we analyzed Homeodomain-interacting protein kinase (Hipk) 2 expression in the embryonic and adult pancreas by in situ hybridization and RT-PCR. Moreover, we functionally characterized the role of HIPK2 in regulating IPF1/PDX1 transcriptional activity by performing transient transfection experiments and RNA interference. We show that Hipk2 is expressed in the developing pancreatic epithelium from embryonic day (e) 12 to e15 but that the expression becomes preferentially confined to pancreatic endocrine cells at later developmental stages. Moreover, we show that HIPK2 positively influences IPF1/PDX1 transcriptional activity and that the kinase activity of HIPK2 is required for this effect. We also demonstrate that HIPK2 directly phosphorylates the C-terminal portion of IPF1/PDX1. Taken together, our data provide evidence for a new mechanism by which IPF1/PDX1 transcriptional activity, and thus possibly pancreas development and/or beta-cell function, is regulated. PMID: 18772243 [PubMed - as supplied by publisher]
Protective role of autophagy in palmitate-induced INS-1 beta cell death.
Choi SE, Lee SM, Lee YJ, Li LJ, Lee SJ, Lee JH, Kim Y, Jun HS, Lee KW, Kang Y Related Articles Protective role of autophagy in palmitate-induced INS-1 beta cell death. Endocrinology. 2008 Sep 4; Authors: Choi SE, Lee SM, Lee YJ, Li LJ, Lee SJ, Lee JH, Kim Y, Jun HS, Lee KW, Kang Y Autophagy, a vacuolar degradative pathway, constitutes a stress adaptation that avoids cell death or elicits the alternative cell-death pathway. This study was undertaken to determine whether autophagy is activated in palmitate-treated beta cells and, if activated, what the role of autophagy is in the palmitate-induced beta cell death. The enhanced formation of autophagosomes and autolysosomes was observed by exposure of INS-1 beta cells to 400 microM palmitate in the presence of 25 mM glucose for 12 hours. The formation of green fluorescent protein (GFP)-LC3-labeled structures (GFP-LC3 dots), with the conversion from LC3-I to LC3-II, was also distinct in the palmitate-treated cells. The phospho-mTOR level, a typical signal pathway that inhibits activation of autophagy, was gradually decreased by palmitate treatment. Blockage of the mTOR signaling pathway by treatment with rapamycin augmented the formation of autophagosomes but reduced palmitate-induced INS-1 cell death. In contrast, reduction of autophagosome-formation by knocking down the ATG5, inhibition of fusion between autophagosome and lysosome by treatment with bafilomycin A1, or inhibition of proteolytic degradation by treatment with E64d/pepstatin A, significantly augmented palmitate-induced INS-1 cell death. These findings showed that the autophagy system could be activated in palmitate-treated INS-1 beta cells and suggested that the induction of autophagy might play an adaptive and protective role in palmitate-induced cell death. PMID: 18772242 [PubMed - as supplied by publisher]
Anti-androgen exposure in utero disrupts expression of desert hedgehog and insulin-like factor 3 in the developing fetal rat testis.
Brokken LJ, Adamsson A, Paranko J, Toppari J Related Articles Anti-androgen exposure in utero disrupts expression of desert hedgehog and insulin-like factor 3 in the developing fetal rat testis. Endocrinology. 2008 Sep 4; Authors: Brokken LJ, Adamsson A, Paranko J, Toppari J Testicular development is an androgen-dependent process and fetal exposure to anti-androgens disrupts male sexual differentiation. A variety of testicular disorders may result from impaired development of fetal Leydig and Sertoli cells. We hypothesised that anti-androgenic exposure during fetal development interferes with desert hedgehog (Dhh) signalling in the testis and results in impaired Leydig cell differentiation. Fetal rats were exposed in utero to the anti-androgen flutamide from 10.5 days post conception (dpc) until sacrifice or delivery. Fetal testes were isolated at different time points during gestation and gene expression levels of Dhh, patched-1 (Ptc1), steroidogenic factor 1 (Sf1), cytochrome P450 side chain cleavage (P450scc), 3beta-HSD type 1 (Hsd3b1) and insulin-like factor 3 (Insl3) were analysed. To study direct effects of hedgehog signalling on testicular development, testes from 14.5 dpc fetuses were cultured for 3 days in the presence of cyclopamine, sonic hedgehog (Shh) or vehicle and gene expression levels and testosterone secretion were analysed. Organ cultures were also analysed histologically and cleaved-caspase 3 immunohistochemistry was performed to assess apoptosis. In utero exposure to flutamide decreased expression levels of Dhh, Ptc1, Sf1, P450scc, Hsd3b1 and Insl3, particularly from 17.5 dpc onwards. Inhibition of hedgehog signalling in testis cultures resulted in similar effects on gene expression levels. Apoptosis in Wolffian ducts was increased by cyclopamine compared to Shh or vehicle treated cultures. We conclude that exposure to the anti-androgen flutamide interferes with Dhh signalling resulting in an impaired differentiation of the fetal Leydig cells and subsequently to abnormal testicular development and sexual differentiation. PMID: 18772241 [PubMed - as supplied by publisher]
Superoxide and Respiratory Coupling in Mitochondria of Insulin Deficient Diabetic Rats.
Herlein JA, Fink BD, O'Malley Y, Sivitz WI Related Articles Superoxide and Respiratory Coupling in Mitochondria of Insulin Deficient Diabetic Rats. Endocrinology. 2008 Sep 4; Authors: Herlein JA, Fink BD, O'Malley Y, Sivitz WI Mitochondrial reactive oxygen species (ROS) have been implicated in both diabetic complications and the progression of the underlying diabetic state. However, it is not clear whether mitochondria of diabetic origin are intrinsically altered to generate excess ROS independent of the surrounding diabetic milieu. Mitochondria were isolated from gastrocnemius, heart, and liver of two-week and two-month streptozotocin (STZ) diabetic rats and controls. We rigidly quantified mitochondrial superoxide, respiration and ATP production, respiratory coupling, the expression of several proteins with antioxidant properties, and the redox state of glutathione. Both fluorescent assessment and electron paramagnetic spectroscopy revealed that superoxide production was unchanged or reduced in the two-month diabetic mitochondria compared to controls. Kinetic analysis of the proton leak showed that diabetic heart and muscle mitochondria were actually more coupled compared to control despite an approximate 2-4 fold increase in uncoupling protein-3 content. Adenine nucleotide translocator type 1 expression was reduced by approximately 50% in diabetic muscle mitochondria. Catalase was significantly upregulated in muscle and heart tissue and in heart mitochondria whereas glutathione peroxidase expression was increased in liver mitochondria of diabetic rats. We conclude that gastrocnemius, heart, and liver mitochondria of STZ-diabetic rats are not irrevocably altered towards excess superoxide production either by complex I or complex III. Moreover, gastrocnemius and heart mitochondria demonstrate increased, not decreased, respiratory coupling. Mitochondria of insulin deficient diabetic rats do show signs of adaptation to antecedent oxidative stress manifested as tissue specific enzyme and uncoupling protein expression but remain remarkably robust with respect to superoxide production. PMID: 18772240 [PubMed - as supplied by publisher]
Different Outcomes of Unliganded and Liganded Estrogen Receptor-alpha on Neurite Outgrowth in PC12 Cells.
Mérot Y, Ferrière F, Gailhouste L, Huet G, Percevault F, Saligaut C, Flouriot G Related Articles Different Outcomes of Unliganded and Liganded Estrogen Receptor-alpha on Neurite Outgrowth in PC12 Cells. Endocrinology. 2008 Sep 4; Authors: Mérot Y, Ferrière F, Gailhouste L, Huet G, Percevault F, Saligaut C, Flouriot G A precise description of the mechanisms by which estrogen receptor-alpha (ERalpha) exerts its influences on cellular growth and differentiation is still pending. Here, we report that the differentiation of PC12 cells is profoundly affected by ERalpha. Importantly, depending upon its binding to 17betaE2, ERalpha is found to exert different effects on pathways involved in the nerve growth factor (NGF) signaling. Indeed, upon its stable expression in PC12 cells, unliganded ERalpha is able to partially inhibit the neurite outgrowth induced by NGF. This process involves a repression of MAPK and PI3K/Akt signaling pathways, which leads to a negative regulation of markers of neuronal differentiation such as VGF and NFLc. This repressive action of unliganded ERalpha is mediated by its D domain and does not involve its transactivation and DNA binding domains, thereby suggesting that direct transcriptional activities of ERalpha is not required. In contrast with this repressive action occurring in the absence of 17betaE2, the expression of ERalpha in PC12 cells allows 17betaE2 to potentiate the NGF-induced neurite outgrowth. Importantly, 17betaE2 has no impact on NGF-induced activity of MAPK and Akt signaling pathways. The mechanisms engaged by liganded ERalpha are thus unlikely to rely on an antagonism of the inhibition mediated by the unliganded ERalpha. Furthermore, 17betaE2 enhances NGF-induced response of VGF and NFLc neuronal markers in PC12 clones expressing ERalpha. This stimulatory effect of 17betaE2 requires the transactivation functions of ERalpha and its D domain, suggesting that an ERE-independent transcriptional mechanism is potentially relevant for the neuritogenic properties of 17betaE2 in ERalpha expressing PC12 cells. PMID: 18772239 [PubMed - as supplied by publisher]
Hypoxia and leucine deprivation induce human IGFBP-1 hyper-phosphorylation and increase its biological activity.
Seferovic MD, Ali R, Kamei H, Liu S, Khosravi JM, Nazarian S, Han VK, Duan C, Gupta MB Related Articles Hypoxia and leucine deprivation induce human IGFBP-1 hyper-phosphorylation and increase its biological activity. Endocrinology. 2008 Sep 4; Authors: Seferovic MD, Ali R, Kamei H, Liu S, Khosravi JM, Nazarian S, Han VK, Duan C, Gupta MB Fetal growth restriction (FGR) is often caused by uteroplacental insufficiency that leads to fetal hypoxia and nutrient deprivation. Elevated IGFBP-1 expression associated with FGR has been documented. In this study, we tested the hypothesis that hypoxia and nutrient deprivation induce IGFBP-1 phosphorylation and increase its biological potency in inhibiting IGF actions. HepG2 cells were subjected to hypoxia and leucine deprivation to mimic the deprivation of metabolic substrates. The total IGFBP-1 levels measured by ELISA were approximately 2 to 2.5-fold higher in hypoxia and leucine deprivation treated cells compared to the controls. 2-D immunoblotting showed that while the non-phosphorylated isoform is the predominant IGFBP-1 in the controls, the highly phosphorylated isoforms were dominant in hypoxia and leucine deprivation treated cells. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed four serine phosphorylation sites: three known sites (pSer 101, pSer 119 and pSer 169) and a novel site (pSer 98). Liquid chromatography-mass spectrometry (LC-MS) was used to estimate the changes of phosphorylation upon treatment. Biacore analysis indicated the highly phosphorylated IGFBP-1 isoforms found in hypoxia and leucine deprivation treated cells had greater affinity for IGF-1 (KD 5.83E-10 M and 6.40E-09 M) relative to the IGFBP-1 from the controls (KD approximately 1.54E -07 M). Furthermore, the highly phosphorylated IGFBP-1 had a stronger effect in inhibiting IGF-I-stimulated cell proliferation. These findings suggest that IGFBP-1 phosphorylation may be a novel mechanism of fetal adaptive response to hypoxia and nutrient restriction. PMID: 18772238 [PubMed - as supplied by publisher]
PubMed: 0804-4643
Management of osteoporosis in children.
Shaw N Related Articles Management of osteoporosis in children. Eur J Endocrinol. 2008 Sep 4; Authors: Shaw N Osteoporosis is being increasingly recognised in paediatric practice as a consequence of several factors. These include the increasing complexity of chronic conditions and the associated treatments managed by paediatricians. In addition the improved care provided to children with chronic illness has led to many of them living long enough to develop osteoporosis. The availability of methods to assess bone density in children as a surrogate marker of bone strength and the possibility of medical treatment to increase bone density has also resulted in an increased awareness of groups of children who may be at risk of osteoporosis. This article reviews the current definition of osteoporosis in children, aetiological factors and the evidence for effective treatment. PMID: 18772270 [PubMed - as supplied by publisher]
Diet or exercise: what is more effective in preventing or reducing metabolic alterations?
Bo S, Ciccone G, Guidi S, Gambino R, Durazzo M, Gentile L, Cassader M, Cavallo-Perin P, Pagano G Related Articles Diet or exercise: what is more effective in preventing or reducing metabolic alterations? Eur J Endocrinol. 2008 Sep 4; Authors: Bo S, Ciccone G, Guidi S, Gambino R, Durazzo M, Gentile L, Cassader M, Cavallo-Perin P, Pagano G Objective/design: The influence of diet and exercise on metabolic syndrome is controversial since fit individuals might also eat healthier foods. We evaluated the association of diet/exercise variation with reductions in metabolic variables and C-reactive protein (CRP) values in the experimental and control arms of a 1-year randomized lifestyle intervention trial performed in patients with multiple metabolic abnormalities. Methods: A prospective study of 169 cases and 166 controls after a lifestyle intervention was performed. Results: In the intervention group, 15/169 (8.9%), 63/169 (37.3%), 70/169 (41.4%) reached only dietary, only exercise, dietary/exercise targets, respectively. Reductions in weight, BMI, and waist were significant only in patients who increased exercise. Most controls did not reach any target (131/166, 78.9%), while only few patients reached only dietary (13/166, 7.8%), only exercise (5/166, 3.0%), and dietary/exercise targets (17/166, 10.2%). Weight, BMI, and waist reduction was more pronounced in those reaching the exercise target. In the whole cohort, increased exercise was inversely associated with weight, BMI, waist, and CRP, increased saturated fat was directly associated with weight, BMI, waist, and diastolic pressure variations, while increased fiber intake was inversely associated with glucose values in a multiple regression model. After adjusting for waist changes, the associations between exercise and CRP (beta= -0.023; 95%CI -0.028 -0.017;p<0.001) and the associations between fiber and glucose (beta= -0.022;-0.031 -0.013;p<0.001) remained significant. Conclusions: Independent of weight reduction, exercise level and fiber intake are inversely associated with CRP, and fasting glucose values, respectively. Change in lifestyle may lower inflammation and prevent metabolic deterioration. PMID: 18772269 [PubMed - as supplied by publisher]
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THE HOMEODOMAIN-INTERACTING PROTEIN KINASE 2 (HIPK2) REGULATES IPF1/PDX1 TRANSCRIPTIONAL ACTIVITY.
Boucher MJ, Simoneau M, Edlund H Related Articles THE HOMEODOMAIN-INTERACTING PROTEIN KINASE 2 (HIPK2) REGULATES IPF1/PDX1 TRANSCRIPTIONAL ACTIVITY. Endocrinology. 2008 Sep 4; Authors: Boucher MJ, Simoneau M, Edlund H The homeodomain transcription factor IPF1/PDX1 plays a crucial role in both pancreas development and maintenance of beta-cell function. Targeted disruption of the Ipf1/Pdx1 gene in beta-cells of mice leads to overt diabetes and reduced Ipf1/Pdx1 gene expression results in decreased insulin expression and secretion. In humans, mutations in the IPF1 gene have been linked to diabetes. Hence, the identification of molecular mechanisms regulating the transcriptional activity of this key transcription factor is of great interest. Herein, we analyzed Homeodomain-interacting protein kinase (Hipk) 2 expression in the embryonic and adult pancreas by in situ hybridization and RT-PCR. Moreover, we functionally characterized the role of HIPK2 in regulating IPF1/PDX1 transcriptional activity by performing transient transfection experiments and RNA interference. We show that Hipk2 is expressed in the developing pancreatic epithelium from embryonic day (e) 12 to e15 but that the expression becomes preferentially confined to pancreatic endocrine cells at later developmental stages. Moreover, we show that HIPK2 positively influences IPF1/PDX1 transcriptional activity and that the kinase activity of HIPK2 is required for this effect. We also demonstrate that HIPK2 directly phosphorylates the C-terminal portion of IPF1/PDX1. Taken together, our data provide evidence for a new mechanism by which IPF1/PDX1 transcriptional activity, and thus possibly pancreas development and/or beta-cell function, is regulated. PMID: 18772243 [PubMed - as supplied by publisher]
Protective role of autophagy in palmitate-induced INS-1 beta cell death.
Choi SE, Lee SM, Lee YJ, Li LJ, Lee SJ, Lee JH, Kim Y, Jun HS, Lee KW, Kang Y Related Articles Protective role of autophagy in palmitate-induced INS-1 beta cell death. Endocrinology. 2008 Sep 4; Authors: Choi SE, Lee SM, Lee YJ, Li LJ, Lee SJ, Lee JH, Kim Y, Jun HS, Lee KW, Kang Y Autophagy, a vacuolar degradative pathway, constitutes a stress adaptation that avoids cell death or elicits the alternative cell-death pathway. This study was undertaken to determine whether autophagy is activated in palmitate-treated beta cells and, if activated, what the role of autophagy is in the palmitate-induced beta cell death. The enhanced formation of autophagosomes and autolysosomes was observed by exposure of INS-1 beta cells to 400 microM palmitate in the presence of 25 mM glucose for 12 hours. The formation of green fluorescent protein (GFP)-LC3-labeled structures (GFP-LC3 dots), with the conversion from LC3-I to LC3-II, was also distinct in the palmitate-treated cells. The phospho-mTOR level, a typical signal pathway that inhibits activation of autophagy, was gradually decreased by palmitate treatment. Blockage of the mTOR signaling pathway by treatment with rapamycin augmented the formation of autophagosomes but reduced palmitate-induced INS-1 cell death. In contrast, reduction of autophagosome-formation by knocking down the ATG5, inhibition of fusion between autophagosome and lysosome by treatment with bafilomycin A1, or inhibition of proteolytic degradation by treatment with E64d/pepstatin A, significantly augmented palmitate-induced INS-1 cell death. These findings showed that the autophagy system could be activated in palmitate-treated INS-1 beta cells and suggested that the induction of autophagy might play an adaptive and protective role in palmitate-induced cell death. PMID: 18772242 [PubMed - as supplied by publisher]
Anti-androgen exposure in utero disrupts expression of desert hedgehog and insulin-like factor 3 in the developing fetal rat testis.
Brokken LJ, Adamsson A, Paranko J, Toppari J Related Articles Anti-androgen exposure in utero disrupts expression of desert hedgehog and insulin-like factor 3 in the developing fetal rat testis. Endocrinology. 2008 Sep 4; Authors: Brokken LJ, Adamsson A, Paranko J, Toppari J Testicular development is an androgen-dependent process and fetal exposure to anti-androgens disrupts male sexual differentiation. A variety of testicular disorders may result from impaired development of fetal Leydig and Sertoli cells. We hypothesised that anti-androgenic exposure during fetal development interferes with desert hedgehog (Dhh) signalling in the testis and results in impaired Leydig cell differentiation. Fetal rats were exposed in utero to the anti-androgen flutamide from 10.5 days post conception (dpc) until sacrifice or delivery. Fetal testes were isolated at different time points during gestation and gene expression levels of Dhh, patched-1 (Ptc1), steroidogenic factor 1 (Sf1), cytochrome P450 side chain cleavage (P450scc), 3beta-HSD type 1 (Hsd3b1) and insulin-like factor 3 (Insl3) were analysed. To study direct effects of hedgehog signalling on testicular development, testes from 14.5 dpc fetuses were cultured for 3 days in the presence of cyclopamine, sonic hedgehog (Shh) or vehicle and gene expression levels and testosterone secretion were analysed. Organ cultures were also analysed histologically and cleaved-caspase 3 immunohistochemistry was performed to assess apoptosis. In utero exposure to flutamide decreased expression levels of Dhh, Ptc1, Sf1, P450scc, Hsd3b1 and Insl3, particularly from 17.5 dpc onwards. Inhibition of hedgehog signalling in testis cultures resulted in similar effects on gene expression levels. Apoptosis in Wolffian ducts was increased by cyclopamine compared to Shh or vehicle treated cultures. We conclude that exposure to the anti-androgen flutamide interferes with Dhh signalling resulting in an impaired differentiation of the fetal Leydig cells and subsequently to abnormal testicular development and sexual differentiation. PMID: 18772241 [PubMed - as supplied by publisher]
Superoxide and Respiratory Coupling in Mitochondria of Insulin Deficient Diabetic Rats.
Herlein JA, Fink BD, O'Malley Y, Sivitz WI Related Articles Superoxide and Respiratory Coupling in Mitochondria of Insulin Deficient Diabetic Rats. Endocrinology. 2008 Sep 4; Authors: Herlein JA, Fink BD, O'Malley Y, Sivitz WI Mitochondrial reactive oxygen species (ROS) have been implicated in both diabetic complications and the progression of the underlying diabetic state. However, it is not clear whether mitochondria of diabetic origin are intrinsically altered to generate excess ROS independent of the surrounding diabetic milieu. Mitochondria were isolated from gastrocnemius, heart, and liver of two-week and two-month streptozotocin (STZ) diabetic rats and controls. We rigidly quantified mitochondrial superoxide, respiration and ATP production, respiratory coupling, the expression of several proteins with antioxidant properties, and the redox state of glutathione. Both fluorescent assessment and electron paramagnetic spectroscopy revealed that superoxide production was unchanged or reduced in the two-month diabetic mitochondria compared to controls. Kinetic analysis of the proton leak showed that diabetic heart and muscle mitochondria were actually more coupled compared to control despite an approximate 2-4 fold increase in uncoupling protein-3 content. Adenine nucleotide translocator type 1 expression was reduced by approximately 50% in diabetic muscle mitochondria. Catalase was significantly upregulated in muscle and heart tissue and in heart mitochondria whereas glutathione peroxidase expression was increased in liver mitochondria of diabetic rats. We conclude that gastrocnemius, heart, and liver mitochondria of STZ-diabetic rats are not irrevocably altered towards excess superoxide production either by complex I or complex III. Moreover, gastrocnemius and heart mitochondria demonstrate increased, not decreased, respiratory coupling. Mitochondria of insulin deficient diabetic rats do show signs of adaptation to antecedent oxidative stress manifested as tissue specific enzyme and uncoupling protein expression but remain remarkably robust with respect to superoxide production. PMID: 18772240 [PubMed - as supplied by publisher]
Different Outcomes of Unliganded and Liganded Estrogen Receptor-alpha on Neurite Outgrowth in PC12 Cells.
Mérot Y, Ferrière F, Gailhouste L, Huet G, Percevault F, Saligaut C, Flouriot G Related Articles Different Outcomes of Unliganded and Liganded Estrogen Receptor-alpha on Neurite Outgrowth in PC12 Cells. Endocrinology. 2008 Sep 4; Authors: Mérot Y, Ferrière F, Gailhouste L, Huet G, Percevault F, Saligaut C, Flouriot G A precise description of the mechanisms by which estrogen receptor-alpha (ERalpha) exerts its influences on cellular growth and differentiation is still pending. Here, we report that the differentiation of PC12 cells is profoundly affected by ERalpha. Importantly, depending upon its binding to 17betaE2, ERalpha is found to exert different effects on pathways involved in the nerve growth factor (NGF) signaling. Indeed, upon its stable expression in PC12 cells, unliganded ERalpha is able to partially inhibit the neurite outgrowth induced by NGF. This process involves a repression of MAPK and PI3K/Akt signaling pathways, which leads to a negative regulation of markers of neuronal differentiation such as VGF and NFLc. This repressive action of unliganded ERalpha is mediated by its D domain and does not involve its transactivation and DNA binding domains, thereby suggesting that direct transcriptional activities of ERalpha is not required. In contrast with this repressive action occurring in the absence of 17betaE2, the expression of ERalpha in PC12 cells allows 17betaE2 to potentiate the NGF-induced neurite outgrowth. Importantly, 17betaE2 has no impact on NGF-induced activity of MAPK and Akt signaling pathways. The mechanisms engaged by liganded ERalpha are thus unlikely to rely on an antagonism of the inhibition mediated by the unliganded ERalpha. Furthermore, 17betaE2 enhances NGF-induced response of VGF and NFLc neuronal markers in PC12 clones expressing ERalpha. This stimulatory effect of 17betaE2 requires the transactivation functions of ERalpha and its D domain, suggesting that an ERE-independent transcriptional mechanism is potentially relevant for the neuritogenic properties of 17betaE2 in ERalpha expressing PC12 cells. PMID: 18772239 [PubMed - as supplied by publisher]
Hypoxia and leucine deprivation induce human IGFBP-1 hyper-phosphorylation and increase its biological activity.
Seferovic MD, Ali R, Kamei H, Liu S, Khosravi JM, Nazarian S, Han VK, Duan C, Gupta MB Related Articles Hypoxia and leucine deprivation induce human IGFBP-1 hyper-phosphorylation and increase its biological activity. Endocrinology. 2008 Sep 4; Authors: Seferovic MD, Ali R, Kamei H, Liu S, Khosravi JM, Nazarian S, Han VK, Duan C, Gupta MB Fetal growth restriction (FGR) is often caused by uteroplacental insufficiency that leads to fetal hypoxia and nutrient deprivation. Elevated IGFBP-1 expression associated with FGR has been documented. In this study, we tested the hypothesis that hypoxia and nutrient deprivation induce IGFBP-1 phosphorylation and increase its biological potency in inhibiting IGF actions. HepG2 cells were subjected to hypoxia and leucine deprivation to mimic the deprivation of metabolic substrates. The total IGFBP-1 levels measured by ELISA were approximately 2 to 2.5-fold higher in hypoxia and leucine deprivation treated cells compared to the controls. 2-D immunoblotting showed that while the non-phosphorylated isoform is the predominant IGFBP-1 in the controls, the highly phosphorylated isoforms were dominant in hypoxia and leucine deprivation treated cells. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed four serine phosphorylation sites: three known sites (pSer 101, pSer 119 and pSer 169) and a novel site (pSer 98). Liquid chromatography-mass spectrometry (LC-MS) was used to estimate the changes of phosphorylation upon treatment. Biacore analysis indicated the highly phosphorylated IGFBP-1 isoforms found in hypoxia and leucine deprivation treated cells had greater affinity for IGF-1 (KD 5.83E-10 M and 6.40E-09 M) relative to the IGFBP-1 from the controls (KD approximately 1.54E -07 M). Furthermore, the highly phosphorylated IGFBP-1 had a stronger effect in inhibiting IGF-I-stimulated cell proliferation. These findings suggest that IGFBP-1 phosphorylation may be a novel mechanism of fetal adaptive response to hypoxia and nutrient restriction. PMID: 18772238 [PubMed - as supplied by publisher]
PubMed: 0804-4643
Management of osteoporosis in children.
Shaw N Related Articles Management of osteoporosis in children. Eur J Endocrinol. 2008 Sep 4; Authors: Shaw N Osteoporosis is being increasingly recognised in paediatric practice as a consequence of several factors. These include the increasing complexity of chronic conditions and the associated treatments managed by paediatricians. In addition the improved care provided to children with chronic illness has led to many of them living long enough to develop osteoporosis. The availability of methods to assess bone density in children as a surrogate marker of bone strength and the possibility of medical treatment to increase bone density has also resulted in an increased awareness of groups of children who may be at risk of osteoporosis. This article reviews the current definition of osteoporosis in children, aetiological factors and the evidence for effective treatment. PMID: 18772270 [PubMed - as supplied by publisher]
Diet or exercise: what is more effective in preventing or reducing metabolic alterations?
Bo S, Ciccone G, Guidi S, Gambino R, Durazzo M, Gentile L, Cassader M, Cavallo-Perin P, Pagano G Related Articles Diet or exercise: what is more effective in preventing or reducing metabolic alterations? Eur J Endocrinol. 2008 Sep 4; Authors: Bo S, Ciccone G, Guidi S, Gambino R, Durazzo M, Gentile L, Cassader M, Cavallo-Perin P, Pagano G Objective/design: The influence of diet and exercise on metabolic syndrome is controversial since fit individuals might also eat healthier foods. We evaluated the association of diet/exercise variation with reductions in metabolic variables and C-reactive protein (CRP) values in the experimental and control arms of a 1-year randomized lifestyle intervention trial performed in patients with multiple metabolic abnormalities. Methods: A prospective study of 169 cases and 166 controls after a lifestyle intervention was performed. Results: In the intervention group, 15/169 (8.9%), 63/169 (37.3%), 70/169 (41.4%) reached only dietary, only exercise, dietary/exercise targets, respectively. Reductions in weight, BMI, and waist were significant only in patients who increased exercise. Most controls did not reach any target (131/166, 78.9%), while only few patients reached only dietary (13/166, 7.8%), only exercise (5/166, 3.0%), and dietary/exercise targets (17/166, 10.2%). Weight, BMI, and waist reduction was more pronounced in those reaching the exercise target. In the whole cohort, increased exercise was inversely associated with weight, BMI, waist, and CRP, increased saturated fat was directly associated with weight, BMI, waist, and diastolic pressure variations, while increased fiber intake was inversely associated with glucose values in a multiple regression model. After adjusting for waist changes, the associations between exercise and CRP (beta= -0.023; 95%CI -0.028 -0.017;p<0.001) and the associations between fiber and glucose (beta= -0.022;-0.031 -0.013;p<0.001) remained significant. Conclusions: Independent of weight reduction, exercise level and fiber intake are inversely associated with CRP, and fasting glucose values, respectively. Change in lifestyle may lower inflammation and prevent metabolic deterioration. PMID: 18772269 [PubMed - as supplied by publisher]
Sites:
American Association of Clinical Endocrinologists: AACE is a professional organization devoted to the field of clinical endocrinology.BMC Endocrine Disorders: Provides original research articles on the prevention, diagnosis and management of endocrine disorders, as well as related molecular genetics, pathophysiology, and epidemiology. For physicians.
Case Studies in Endocrine Disorders: Covers evaluation of pituitary, thyroid, parathyroid, adrenal, and reproductive endocrinology topics. Aimed at physicians.
Endo Leaders: An educational resource which discusses the diagnosis, treatment, and long-term complications of untreated adult growth hormone deficiency.
Endocrine and Metabolic Diseases: Patient information on a variety of endocrine disorders.
EndocrineWeb: Large award winning site written by doctors and patients FOR PATIENTS. Over 200 pages and illustrations for thyroid, parathyroid and adrenal. Find a local doctor, support group or join the chat rooms. Updated daily, includes the newest treatments; new pages weekly.
Endocrinology: Detailed information on endocrine disorders
Endotext.org: complete source on Endocrinology, authoritative, constantly up-dated, down-loadable, free, for MDs worldwide
Hypothalamic Hamartoma Support Page: Resources for children and families dealing with this rare endocrine tumor. Information about the function of the hypothalamus, symptoms, treatments, and personal stories. Includes MRI images.
Pathophysiology of the Endocrine System: Presents a tour on the mechanisms of hormone action.
The Endocrine Society: Home Page for The Endocrine Society
The Merck Manual: Endocrine and Metabolic Disorders: Chapters on a variety of endocrine problems such as hyperlipidemia, polyglandular deficiency syndromes, the porphyrias, amyloidosis, and others.
This directory is based on the Open Directory and may have been modified