Реферат
Erythropoietin (EPO) has been well characterized as a renal glycoprotein hormone regulating red blood cell production by inhibiting apoptosis of erythrocyte progenitors in hematopoietic tissues. EPO exerts regulatory effects in cardiac and skeletal muscles. Duchenne muscular dystrophy is a lethal degenerative disorder of skeletal and cardiac muscle. In this study, we tested the possible therapeutic beneficial effect of recombinant EPO (rhEPO) in dystrophic muscles in mdx mice. Total strength was measured using a force transducer coupled to a computer. Gene expression for myostatin, transforming growth factor-β1 (TGF-β1), and tumor necrosis factor-α (TNF-α) was determined by quantitative real time polymerase chain reaction. Myostatin expression was significantly decreased in quadriceps from mdx mice treated with rhEPO (rhEPO=0.60±0.11, control=1.07±0.11). On the other hand, rhEPO had no significant effect on the expression of TGF-β1 (rhEPO=0.95±0.14, control=1.05±0.16) and TNF-α (rhEPO=0.73±0.20, control=1.01±0.09). These results may help to clarify some of the direct actions of EPO on skeletal muscle.
Тема - темы
Animals , Male , Down-Regulation/drug effects , Erythropoietin/therapeutic use , Gene Expression/drug effects , Muscular Dystrophy, Duchenne/drug therapy , Myostatin/metabolism , Recombinant Proteins/therapeutic use , Disease Models, Animal , Dystrophin/deficiency , Mice, Inbred mdx , Muscle Strength/drug effects , Muscle, Skeletal/metabolism , Muscular Dystrophy, Duchenne/metabolism , Myostatin/genetics , Phenotype , Real-Time Polymerase Chain Reaction , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismРеферат
Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g) and triiodothyronine (0.5-50 µg/100 g) for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P) days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold). Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60%) ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold), and decreased heart rate (5%), fast muscle myoglobin mRNA (30%) and body weight (20%) in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30%) and body weight (14%). These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.
Тема - темы
Animals , Male , Hyperthyroidism/metabolism , Hypothyroidism/metabolism , Muscle, Skeletal/metabolism , Myocardium/metabolism , Myoglobin/genetics , RNA, Messenger/metabolism , Animals, Newborn , Antithyroid Agents , Blood Pressure , Blotting, Northern , Gene Expression , Heart Rate , Heart Ventricles/metabolism , Hyperthyroidism/chemically induced , Hypothyroidism/chemically induced , Myoglobin/metabolism , Organ Size , Propylthiouracil , Random Allocation , Rats, Wistar , Reactive Oxygen Species , TriiodothyronineРеферат
The amino acid arginine (Arg) is a recognized secretagogue of growth hormone (GH), and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO), which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (~250 g) were removed, divided into two halves, pooled (three hemi-pituitaries) and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM), the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM) and a cyclic guanosine monophosphate (cGMP) analogue (8-Br-cGMP, 1 mM) increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM) blunted the effect of SNP, and the combined treatment with Arg and L-NAME (a NO synthase (NOS) inhibitor, 55 mM) abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM) also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression.
Тема - темы
Animals , Male , Rats , Arginine/pharmacology , Gene Expression Regulation/drug effects , Growth Hormone/genetics , Pituitary Gland/drug effects , Dose-Response Relationship, Drug , Growth Hormone/metabolism , Nitric Oxide Synthase/drug effects , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/metabolism , Nitric Oxide/genetics , Nitric Oxide/metabolism , Pituitary Gland/metabolism , Rats, Wistar , Signal TransductionРеферат
The actions of thyroid hormone (TH) on pancreatic beta cells have not been thoroughly explored, with current knowledge being limited to the modulation of insulin secretion in response to glucose, and beta cell viability by regulation of pro-mitotic and pro-apoptotic factors. Therefore, the effects of TH on proinsulin gene expression are not known. This led us to measure: a) proinsulin mRNA expression, b) proinsulin transcripts and eEF1A protein binding to the actin cytoskeleton, c) actin cytoskeleton arrangement, and d) proinsulin mRNA poly(A) tail length modulation in INS-1E cells cultured in different media containing: i) normal fetal bovine serum - FBS (control); ii) normal FBS plus 1 µM or 10 nM T3, for 12 h, and iii) FBS depleted of TH for 24 h (Tx). A decrease in proinsulin mRNA content and attachment to the cytoskeleton were observed in hypothyroid (Tx) beta cells. The amount of eEF1A protein anchored to the cytoskeleton was also reduced in hypothyroidism, and it is worth mentioning that eEF1A is essential to attach transcripts to the cytoskeleton, which might modulate their stability and rate of translation. Proinsulin poly(A) tail length and cytoskeleton arrangement remained unchanged in hypothyroidism. T3 treatment of control cells for 12 h did not induce any changes in the parameters studied. The data indicate that TH is important for proinsulin mRNA expression and translation, since its total amount and attachment to the cytoskeleton are decreased in hypothyroid beta cells, providing evidence that effects of TH on carbohydrate metabolism also include the control of proinsulin gene expression.
Тема - темы
Animals , Cattle , Rats , Actin Cytoskeleton/metabolism , Eukaryotic Initiation Factor-1/metabolism , Hypothyroidism/metabolism , Insulin-Secreting Cells/metabolism , Proinsulin/genetics , RNA, Messenger/metabolism , Gene Expression , Hypothyroidism/genetics , Proinsulin/biosynthesis , RNA, Messenger/geneticsРеферат
The maxilla and masseter muscles are components of the stomatognathic system involved in chewing, which is frequently affected by physical forces such as gravity, and by dental, orthodontic and orthopedic procedures. Thyroid hormones (TH) are known to regulate the expression of genes that control bone mass and the oxidative properties of muscles; however, little is known about the effects of TH on the stomatognathic system. This study investigated this issue by evaluating: i) osteoprotegerin (OPG) and osteopontine (OPN) mRNA expression in the maxilla and ii) myoglobin (Mb) mRNA and protein expression, as well as fiber composition of the masseter. Male Wistar rats (~250 g) were divided into thyroidectomized (Tx) and sham-operated (SO) groups (N = 24/group) treated with T3 or saline (0.9 percent) for 15 days. Thyroidectomy increased OPG (~40 percent) and OPN (~75 percent) mRNA expression, while T3 treatment reduced OPG (~40 percent) and OPN (~75 percent) in Tx, and both (~50 percent) in SO rats. Masseter Mb mRNA expression and fiber type composition remained unchanged, despite the induction of hypo- and hyperthyroidism. However, Mb content was decreased in Tx rats even after T3 treatment. Since OPG and OPN are key proteins involved in the osteoclastogenesis inhibition and bone mineralization, respectively, and that Mb functions as a muscle store of O2 allowing muscles to be more resistant to fatigue, the present data indicate that TH also interfere with maxilla remodeling and the oxidative properties of the masseter, influencing the function of the stomatognathic system, which may require attention during dental, orthodontic and orthopedic procedures in patients with thyroid diseases.
Тема - темы
Animals , Male , Rats , Masseter Muscle/drug effects , Maxilla/drug effects , Myoglobin/metabolism , Osteopontin/metabolism , Osteoprotegerin/metabolism , Thyroid Hormones/physiology , Triiodothyronine/pharmacology , Blotting, Northern , Hyperthyroidism/physiopathology , Masseter Muscle/anatomy & histology , Masseter Muscle/metabolism , Maxilla/metabolism , Myoglobin/genetics , Osteopontin/genetics , Osteoprotegerin/genetics , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , RNA , RNA, Messenger/metabolism , Thyroidectomy , Thyroid Hormones/metabolismРеферат
In order to investigate the role of serotonin in the regulation of thyrotropin (TSH) secretion, control and propylthiouracil (PTU)treated male Wistar rats weighing approximately 250 g were subjected to ip injections of methysergide (MET, 10 mug/l00 g body weight), a serotonergic receptor blocker, and killed 60 min later by decapitation. Serum and pituitary concentrations of TSH were measured by radioimmunoassay. In addition, the pituitary release of TSH was estimated in an in vitro system in which pituitary glands were incubated with hypothalamic extracts. MET treatment led to a decrease in pituitary (94.12 ñ 18.55 vs 199.30 ñ 31.47 mug/mg, N = 20), and serum (l.95 ñ 0.92 vs 4.26 ñ 1.40 ng/ml, N = 20) TSH concentration (PТема - темы
Animals
, Male
, Rats
, Methysergide/pharmacology
, Propylthiouracil/pharmacology
, Serotonin/pharmacology
, Thyrotropin-Releasing Hormone/metabolism
, Thyrotropin/metabolism
, Analysis of Variance
, Hypothalamus/metabolism
, Radioimmunoassay
, Rats, Wistar
, Reproducibility of Results
, Thyrotropin-Releasing Hormone/blood
, Thyrotropin-Releasing Hormone/drug effects
, Thyrotropin/blood
, Thyrotropin/drug effects
Реферат
Growth hormone (GH) gene expression was examined in male Wistar rats (200 g) subjected to different manipulations of thyroid status. Thyroidectomy followed by 10 days of treatment with 0.03 methimazole added to drinking water caused a marked decrease in GH mRNA levels estimated by Northern Blot analysis. T3 administration (100 micrograms/100 g body weight, ip, twice daily) to euthyroid rats for one week caused a substantial increase in GH mRNA levels. In another set of experiments, thyroidectomized methimazole-treated rats were killed at different times after a single T3 injection (100 micrograms/100 g body weight, ip). T3 induced a prompt response in GH gene expression by 15 min that reached a maximum after 1 h, remaining so up to 4 h. We conclude that in the rat, GH gene expression is highly dependent on thyroid hormones. Because of the rapidity of the response, the effect is probably mediated by a transcriptional mechanism.
Тема - темы
Animals , Male , Rats , Gene Expression , Growth Hormone , Thyroid Hormones/physiology , Blotting, Northern , Thyroid Hormones/genetics , Thyroid Hormones/metabolism , Rats, Wistar , RNA, Messenger , Time Factors , Transcription, Genetic , Triiodothyronine, ReverseРеферат
the present study examines the metabolic changes caused by chronic mast cell degranulation in rats. There groups of 5 adult rats each were used: 1) rats treated with increasing foses of BW 48/80 (2 to 6 mg/Kg-1 day-1, ip, for 4 days); 2) a control group receiving daily saline injections, and 3) rats treated with disodium chromoglycate (DCG) (40 mg Kg-1 day-1, ip, for 4 days). The third group was included as a control since DCG blocks mast cell degranulation. Saline - and DCG-treated rats showed little differences except for an increase in spleen wet weight and liver glycogen content in the latter. Chronic treatment with compound BW 48/80 resulted in statistically significant changes such as body weight loss, reduction in thymus and spleen wet weights, decrease in spleen protein content, liver glycogen and blood insulin concentrations, increase in plasma free acids fatty acids concentration and adrenal wet weight compared to control rats. These metabolic changes are similar to those reported for hyperthyroidism and support previous findings on the possible role of mast cells in the control of thyroid function
Тема - темы
Rats , Animals , Male , Thyroid Gland , Hyperthyroidism/chemically induced , Mast Cells/drug effects , p-Methoxy-N-methylphenethylamine/adverse effectsТема - темы
Rats , Animals , Male , Cold Temperature , Thyroid Gland/physiology , Thyroxine/metabolism , Triiodothyronine/biosynthesis , Acclimatization , Kidney/metabolism , Liver/metabolism , Rats, Inbred Strains , Thyroidectomy , Thyrotropin/blood , Triiodothyronine, Reverse/blood , Triiodothyronine/bloodРеферат
O metabilismo periferico dos hormonios tiroidianos foi estudado em suspensoes de leucocitos humanos, determinando-se, por radioimunoensaio, agestao in vitro de T3 e rT3 a partir de T4 nao radioativo. Pode-se evidenciar, nas suspensoes de leucocitos provenientes de pacientes portadores de hipertiroidismo, maior geracao in vitro de T3 e rT3, enquanto que diminuicao significativa foi observada nos pacientes com hipotiroidismo. Essas alteracoes sao aparentemente devidas ao excesso e a falta de hormonios tiroidianos, respectivamente, ja que em ambos os casos elas puderam ser revertidas pelo tratamento clinico adequado